Viral Vectors for Gene Therapy the Art of Turning Infectious Agents Into Vehicles of Therapeutics
Open admission peer-reviewed chapter - ONLINE First
Viral Vectors in Gene Therapy and Clinical Applications
Submitted: December 22nd, 2021 Reviewed: January 10th, 2022 Published: March 31st, 2022
DOI: 10.5772/intechopen.102559
From the Edited Volume
Molecular Cloning [Working Title]
Sadik Dincer, Dr. Hatice Aysun Merci̇mek Takci and Dr. Melis Sümengen Özdenefe
IntechOpen Downloads
thirteen
Full Affiliate Downloads on intechopen.com
Abstruse
Developments in cistron therapy, coupled with advances in genome sequencing and a greater understanding of Deoxyribonucleic acid sequences, take given rise to an heady area of research. The apply of viral vectors in gene therapy has get a very promising and fast-emerging technology over the past few decades. Despite previous setbacks, the approval of viral vector therapies worldwide, with many in tardily-stage clinical trials has led to a pregnant increase in research in this expanse of gene therapy. Retroviral, adenoviral, adeno-associated viral, and lentiviral vectors are all cardinal vectors currently being researched and used in clinical trials. There are many challenges with the use of viral vectors that are notwithstanding to be overcome including price of production, the immune response, and the ability to precisely regulate the expression of the transgene. Nonetheless, with increased numbers of clinical trials showing efficacy, safety, and growing financial investment, the future apply of viral vectors in factor therapy is increasingly promising.
Keywords
- cistron therapy
- viral vector
- clinical trials
- approved therapies
- vector production
*Address all correspondence to: ann.simpson@uts.edu.au
i. Introduction
Gene therapy, defined as the delivery of specific genes to a target jail cell to care for a disorder, is a promising molecular applied science that has quickly become a prominent surface area of research. Clinical disorders that could be treated using gene therapy include astringent combined immunodeficiency (SCID), haemophilia, retinitis pigmentosa, diabetes, and various types of cancers [1, 2, 3]. With our increasing agreement of gene function and interactions, as well as the greater availability of genome sequencing, our noesis of how Dna sequences can be used to treat or cure diseases caused past genetic dysfunction has adult greatly.
The commitment of specific genetic material into a host cell requires the apply of a vector, or vehicle, for the transfer of a transgene to a specific jail cell type, past either viral or non-viral means. Techniques for the delivery of not-viral vectors include electroporation, lipofection, and microRNA, which are all useful cistron therapy methods equally they carry decreased biological risk, offer reduced immunogenicity, and price less in both money and fourth dimension to produce when compared to viral vectors [4]. Nevertheless, the ability of a not-viral vector to enter a cell by transfection is not as efficient as viral vectors, accordingly, research over past decades has been more focused on the apply of viral vectors and this is the focus of this review [5].
Mutual viruses that have been used as vectors include adenovirus, adeno-associated virus, retrovirus, and lentivirus [6, 7, eight, ix]. While in that location accept been limitations associated with the use of these viruses, further research, and enhancements in their construction will likely permit their use in a clinical setting. In fact, there are currently several clinical trials using viral vectors in cistron therapy for diverse weather worldwide [10]. The successful utilize of viral vectors in tardily-phase clinical trials and laboratory settings has facilitated growing investment from venture-capital firms and increasing acquisitions of cistron therapy start-ups from pharmaceutical companies [xi]. The increasing focus on, and investment in viral vectors in factor therapy is a very promising sign for their future utilise.
This affiliate provides a summary of different viral vectors currently being investigated for use in factor therapy. Information technology besides provides a review of the different clinical applications of these viral vectors and addresses the advantages and limitations of their utilize. Successes observed using these vectors and the limitations that this area is currently facing are also discussed.
Advertising
2. Viral vectors
Viruses accept evolved structural characteristics that let them to efficiently enter a host cell and replicate effectively [12]. We are positioned to exploit these features to produce safety vectors for clinical utilise, while still maintaining the ability of a virus, carrying a transgene, to enter a host cell. This offers tremendous potential for very impactful therapies for a range of diseases. A viral vector is broadly fabricated-up of three different components, which will vary depending on the type of virus from which information technology is derived [13]. These essential components include an envelope, the desired transgene (which is encapsulated past the envelope), and a regulatory cassette consisting of a grouping of genes that control the expression of the transgene. The incorporation of all of these components to form a vector system is outlined in Figure 1.
Effigy 1.
Production of viral vectors for both
Viral vectors have been used in clinical trials over the past four decades with various levels of success. In 1999, a clinical trial participant died later receiving an adenoviral vector to care for partial ornithine transcarbamylase (OTC) deficiency. The patient suffered a systemic pro-inflammatory response, causing multiple organ system failures [14]. In some other clinical trial, success was observed when a patient with X-linked severe combined immunodeficiency (SCID X1) was treated by retrovirus-mediated gene transfer to CD34 bone marrow cells [15]. However, in other patients in the trial, this handling triggered the evolution of leukaemia [sixteen]. These negative outcomes reduced both funding and confidence in gene therapy, specially adenoviral and retroviral-based vector systems. Despite this, research has continued to better understand the safety and efficacy of viral vectors to make them a viable clinical option. The viral vectors that take been nearly intensively researched are retroviral, adenoviral, adeno-associated, and lentiviral vectors.
2.ane Retroviral vectors
Retroviruses possess two copies of single-stranded RNA, coding for the viral proteins; group antigens (gag), DNA polymerase (pol), and the viral envelope (env). The RNA strands are encapsulated past a glycoprotein envelope which allows this virus to enter a target jail cell. One time internalised, the viral genome integrates inside the host Deoxyribonucleic acid, forming a provirus [8]. Viral proteins are then able to be transcribed and translated, after which they exit the cell. Due to their power to effectively enter a target cell, retroviral vectors are i of the nigh widely used viral vectors in cistron therapy. Retroviral vectors are developed from a disabled murine virus and can but transduce dividing cells [17]. Retroviral vectors have been benign in gene therapy as they tin integrate into the host jail cell genome, assuasive for sustained factor expression. However, the production of viral proteins poses the run a risk of insertional mutagenesis occurring, potentially leading to neoplasm development. This was axiomatic in 2003 when this type of vector was used in a clinical trial for the treatment of (SCID)-X1 disease in which four participants developed leukaemia 3 years after treatment [16]. This was due to the activation of a cellular oncogene during retroviral-vector integration. This raised concerns surrounding the biosafety of this vector and caused a re-evaluation of the apply of retroviral vectors in factor therapy, thereby shifting the focus to culling viral vector systems.
2.2 Adenoviral vectors
Adenoviruses are not-enveloped, double-stranded DNA viruses which are members of the Adenoviridae family [18]. In that location are at least 47 man adenovirus types, which commonly cause conjunctival and respiratory diseases [6]. Human adenoviruses are ubiquitous in the environment; therefore most people volition have immunity to the virus. Infection is usually only mild, simply in immunosuppressed individuals, it can be astringent. Dissimilar retroviral vectors, adenoviral vectors can transfer genes to both dividing and not-dividing cells and possess a relatively large cassette capacity (eight kB). They can too be produced in high titres and deliver genes at a loftier multiplicity of infection [17, xix]. Due to these properties, they have been one of the most common viral vectors used in
2.iii Adeno-associated viral vectors
Adeno-associated viruses (AAV) are pocket-size, non-enveloped virions containing single-stranded DNA molecules. These viruses are members of the
2.4 Lentiviral vectors
Lentiviruses are RNA viruses that are members of the Retroviridae family. Infection with lentiviruses can lead to many types of diseases, including neurological disorders, arthritis, and immunodeficiency. Lentiviruses have glycoproteins on their surface allowing them to gain entry into a diversity of cell types [24]. Like retroviral vectors, they possess the viral genes gag, pol, and env, which allow survival and replication of the lentivirus, as well equally the tat and rev genes, which heighten factor transcription and spread of the virus [25]. Being quite a virulent pathogen, fears of a replication-competent vector forming through the use of lentiviral vectors has reduced their applications in the past.
Lentiviral vectors can transduce both dividing and non-dividing cells, thereby making them an platonic choice for a range of gene delivery applications. Additionally, the lentiviral vectors practise non elicit a strong immune response, therefore, these are a favourable option for clinical application. These vectors permit for long-term transgene expression every bit they integrate into the host genome, and insertion is less likely to occur in close proximity to proto-oncogenes, therefore, limiting the risk of insertional mutagenesis [26]. About lentiviral vectors have been developed from the human immunodeficiency virus (HIV), which has led to some biosafety concerns.
To improve the prophylactic profile of lentiviral vectors, the second-generation vectors have one packaging plasmid which encodes the gag, pol, rev, and tat genes, and the boosted accompaniment virulence factors have been removed. Although the deletion of accessory factors represents a significant improvement to the original vector arrangement, there is notwithstanding a risk for the generation of a recombinant virus. To combat this, in the third-generation lentiviral vectors the packaging plasmid has been dissever further, with the gag and political leader genes independent in one packaging plasmid, rev in another, and env in a third plasmid [27, 28]. Past doing this, the chances of a recombinant virus forming are extremely depression. The tertiary-generation vectors are also self-inactivating due to deletions in the iii'LTR in the vector plasmid, thereby, preventing continuous virus replication. The use of a third-generation, self-inactivating lentiviral vector, as opposed to the second-generation vectors, significantly reduces the biosafety risk of viral replication and development of HIV through the removal of the long terminal repeat promoter [ix].
Advert
three. Applications and clinical use of viral vectors
Over the past four decades, the number of clinical trials using viral vectors for cistron therapy has grown significantly. Throughout this time, there take been many significant discoveries, as well every bit many setbacks. Despite these early obstacles, intensive research in this surface area has connected, and these efforts have led to the approving of many viral vector-based therapies, with many others currently undergoing belatedly-stage clinical trials [ten]. These therapies are predominately focused on treating unlike cancers, besides as a smaller number focused on the handling of monogenic, cardiovascular, and infectious diseases. Over the by two decades, over xx viral vector-based therapies take been approved, 7 of which are adenoviral, adeno-associated, and lentiviral vector-based therapies [29].
3.1 Canonical viral-vector therapies
In the early 1990s, an adenoviral vector was approved for use in clinical trials, representing ane of the get-go viral vectors to achieve such approval [xxx]. Since then, some adenoviral vectors take been approved for widespread use. 'Gendicine' was the beginning approved viral vector engineering, and was canonical in 2003 by the Red china Food and Drug Assistants (FDA) to treat patients with head and neck squamous cell carcinoma [31]. Gendicine is a recombinant adenovirus that expresses the tumour-suppressing protein, p53. Equally of 2020, 30,000 patients had been treated with Gendicine with significantly higher patient response rates observed when it was used in conjunction with chemotherapy, radiotherapy, and other conventional treatments. The clinical outcomes incorporating this viral organization with traditional treatments were more efficacious than the use of traditional treatments lone [32]. Many cancerous tumours occur as a result of mutations to the p53 gene, therefore many clinical studies are currently in progress and the use of Gendicine is becoming increasingly widespread for the treatment of other types of cancers, including breast, liver, pancreas, and colorectal cancers [32]. Another adenoviral vector-based therapy, called Oncorine, was approved past the Chinese FDA in 2005 [33]. Oncorine is used to care for late-stage refractory nasopharyngeal cancer and has been very successful when used in conjunction with chemotherapy and radiotherapy. Due to a deletion in the E2B 55K regions, the vector tin can only infect and replicate in p53 deficient cells, leading to oncolysis of these cells [34].
The AAV vectors have not been intensively researched for as long equally the adenoviral vectors, however, they take been extremely successful since their discovery in the 1960s [35]. At that place have been three AAV vector-based treatments canonical, with two of them remaining on the market. Glybera is an AAV vector-based therapy, which was approved past the European Medical Agency in 2012. Glybera delivers lipoprotein lipase to patients who have lipoprotein lipase deficiency [36]. Although this treatment was able to effectively care for the affliction, information technology was not economically feasible to maintain it on the market place considering the incidence of this disorder is one in 1 million, and consequently it was discontinued in 2017 [37]. Luxturna is some other AAV vector therapy that was granted blessing past the FDA in the United States in 2017 [38]. It is prescribed for patients with an inherited retinal disease called Lebers congenital amaurosis, which causes progressive blindness. Luxturna is also a very expensive treatment ($425,000 per heart). However, because more people are affected by Lebers built amaurosis, the product has remained on the market place [39]. Another AAV vector treatment that has been successful, despite being very expensive, is Zolgensma, which is used to treat patients with spinal muscular cloudburst. The therapy works by delivering a motor neuron survival transgene to replace the non-functional gene in patients. It was canonical in 2019 by the FDA and has seen patients improve to a point where they can walk unsupported, which had not been possible before the advent of this treatment [40].
Like to AAV vectors, lentiviral vectors have not been researched for every bit long equally other vector systems, but from the time of their first use in clinical trials in 2003 they have been very successful [41]. Kymriah was approved by the FDA in 2017 for the treatment of paediatric relapsed B-prison cell acute lymphoblastic leukaemia [42]. Kymriah was the first lentiviral vector-based gene therapy handling and the first chimeric antigen receptor (CAR) T prison cell immunotherapy. This blazon of cancer therapy allows the genetic engineering science of a patient'southward own T cells
three.ii Viral vector therapies in clinical trials
There have been over 3000 approved, ongoing, or completed clinical trials involving the use of viral vectors for gene therapy in the past four decades [45]. The range of disorders being researched for treatment development has expanded with continued research success in the expanse of gene therapy. Clinical trials of gene therapy for many different types of cancers are currently in progress, including head and cervix, lung, ovarian, breast, prostate, hepatocellular carcinoma, and melanoma. A number of monogenic diseases accept also been investigated, including SCID-X1, ADA-SCID, mucopolysaccharidosis, and Fanconi anaemia, as well every bit infectious diseases such equally HIV and most recently, COVID-19 [45]. Retroviral, adenoviral, adeno-associated, and lentiviral vectors make upwardly over one-half of the 3000 clinical trials and every bit stated above have translated into approved therapeutic treatments that have become bachelor on the market. Looking at the trends in the current clinical trial information, much can be deduced regarding the direction of the future of viral vector-based cistron therapy (Figure two).
Figure two.
During the 1990s, retroviral vectors were the most common viral vector used in clinical trials for several disorders, including different cancer types, monogenic diseases, and HIV (Figure 2a). Despite being the about popular choice of viral vector 30 years ago, the use of retroviral vectors has been steadily declining. This miracle is well-nigh likely attributed to its disability to be used in non-dividing cells and a meaning risk of insertional oncogenesis, leading to cancerous jail cell formation [xv]. Despite the completion of 536 clinical trials using a retroviral vector, this has non resulted in any retroviral vector-based gene therapy being currently available on the market place [45]. One handling, called Strimvelis, was on the marketplace but has since been removed. Strimvelis was approved by the European Medicines Agency in 2016 as a treatment for ADA-SCID using a retroviral vector to evangelize adenosine to a patient's cells by
Of all the viral vectors, adenoviral vectors have been almost usually used in clinical trials with 573 either canonical, in progress or completed (Effigy 2b). With two therapies currently on the market place for cancer handling and ii more in late-stage clinical trials, adenoviral vector research and cistron therapy approaches are demonstrating considerable success [45]. With 70% of the clinical trials being for cancer treatments, adenoviral vectors have become the most pop viral vector used in cancer cistron therapy worldwide [45]. Adenoviral vectors are a popular choice for cancer treatment because of their high immunogenicity. While not beneficial in other contexts, the induction of a robust pro-inflammatory response is highly advantageous for cancer treatment [47]. However, similar retroviral vectors, adenoviral vector use has declined in the past decade [10]. This may exist considering of their lack of translation to belatedly-stage clinical trials, and an increase in the utilize of both adeno-associated and lentiviral vectors in gene therapy clinical trials.
Adeno-associated viral vectors have been used in a limited number of clinical trials, as compared to other vector systems, yet, this has not limited their clinical success. The final decade has seen two AAV-vector-based therapies enter the market, besides as a precipitous increment in phase I and phase II clinical trials (Figure 2c). Although many of the AAV vector phase I trials did not begin every bit early as the other vector trials, they at present have the virtually phase III trials approved, ongoing, or completed as of 2021 (Figure 2c). AAV vectors accept also shown clinical efficacy in a range of diseases, including antitrypsin deficiency, ocular diseases, and haemophilia [48, 49, 50, 51]. Seeing the strides AAV vectors have made in but the past two decades, they appear to be a promising technology for time to come employ. Another promising engineering when reviewing clinical trial data is lentiviral vectors. Lentiviral vectors have had the greatest number of clinical trials approved, ongoing, or completed in the by decade despite having the smallest number before 2010 (Figure 2d). Some disorders that lentiviral vector use is primarily focused on include cancers, β-thalassemia, HIV, and Fanconi Anaemia. The benefits of using a lentiviral vector over a retroviral vector for transgene delivery is that they tin transduce slow dividing or non-dividing cells and seem to have less analogousness for integration into oncogenetic sites, particularly the self-inactivating, third-generation lentiviral vectors [52, 53]. These lentiviral vectors with a strong promotor largely mitigate the chance of insertional mutagenesis, however, this take a chance is not eliminated completely. A self-inactivating lentiviral vector has been used in clinical trials for the handling of HIV with a total of 65 patients treated with the vector and no adverse events reported for more than viii years after vector infusion [41]. Analysing both the limited numbers of adverse events and the successful clinical trial data over the past three decades reveals that both AAV and lentiviral vectors are favourable factor therapy technologies for the future.
Advertising
4. Concerns facing viral vector-based gene therapy
Despite their growing success in gene therapy clinical trials, there are still many bug that viral vector applied science will need to overcome to be accepted as a widespread therapeutic option. Key areas of concern with the use of viral vectors are the consecration of an allowed response when delivered
4.1 Immune response
The immunogenicity of a viral vector is measured both quantitatively by the magnitude of the immune response over fourth dimension, and qualitatively by the types of allowed responses that are initiated [54]. Many factors decide the immunogenicity of a vector, and information technology varies greatly depending on the structure of the viral vector system. It is crucial to understand the interaction of the vector with the allowed system before entering clinical trials every bit the occurrence of a severe immune response upon injection tin can effect in many severe complications, and, in some instances, death [55].
Adenoviral and adeno-associated viral vectors are of item immunological business organization. The prevalence of dissimilar adenovirus serotypes varies regionally. For instance, serotype v (Ad5) has a 50% prevalence in America, merely in Africa, this approximates 100% [56]. Despite such variations, adenoviruses are more often than not prevalent in the surround and are highly immunogenic, which can nowadays concerns when administering vectors using the same serotype [57]. If a patient has already been exposed to the serotype used in the therapeutic vector, this is probable to cause a robust immune response characterised by a rapid influx of pre-existing neutralising antibodies to the injection site, thereby reducing the therapeutic dose and limiting the ability of the vector to exert its clinical effect, and causing prophylactic concerns for the patient due to complement activation and resultant inflammation [55]. This is a like situation for AAV as approximately 80% of the worldwide population has already been exposed to an AAV serotype [58]. Previous exposure to serotypes will bear witness to be a major hurdle to overcome in clinical trials for both adenoviral and AAV vectors. In some cases, however, a highly immunogenic vector can be beneficial for the treatment of certain disorders. Adenoviral vectors are the most common vector for cancer therapy mostly due to their highly immunogenic nature. Triggering an anti-tumour response through oncolytic adenovirus handling has proven to evidence some success in treating malignant tumours with two canonical cancer treatments on the market [59].
Lentiviral vectors have a very favourable immunogenic profile, as compared to adenoviral vectors, and this is a notable reason why they take been a popular vector choice in the past decade. Lentiviral infection in humans is quite limited, and, therefore, only a minor per centum of individuals volition carry pre-existing antibodies to the virus. Additionally, in many lentiviral vector systems, the original viral envelope for the Vesicular Stomatitis Virus envelope glycoprotein (VSV-G) has been substituted [24]. Lentiviral vectors trigger long-lasting T-cell immunity, without causing an agin vector-specific amnesty or inflammatory reaction [60], thereby favouring clinical applications.
4.two Cost of production
The price to produce a viral vector is an important consideration if the finish goal is the clinical application [61]. In that location are many costs to consider in the product of a viral vector arrangement, including equipment, laboratory material, purification, storage, and the corporeality of labour needed. As exemplified past the AAV vector-based gene therapy, Glybera, if the product is too expensive to produce and the number of patients affected by the disorder is too low, it may not be economically feasible for the product to stay on the marketplace. A major factor in the toll of production of a vector is the dosage required for 1 patient. For example, a low inoculation dose tin can offset a big production cost [62]. One fashion to lower the price and fourth dimension to produce a big amount of the vector is for the vector to accept a loftier titre level. Adenoviral vectors are very efficient at factor transfer, so the titres for these vectors are very high, which is benign when produced on a large scale [61]. Adenoviral vectors are a very popular choice for vaccinations, and this aspect of their high titre capability is part of the reason for their popularity. Overall, the toll to produce viral vectors is a significant hurdle that will have to exist overcome if they are to be used on a commercial scale. There is currently pregnant research dedicated to streamlining the process of vector production to lower the cost and fourth dimension required for production and to allow product in low-resource areas. This discussion is beyond the scope of this review; even so, it has been considered elsewhere [63, 64, 65].
4.3 Expression of the transgene
Another consideration for viral vector utilize is the commitment of the transgene and to what degree this procedure tin can be controlled. The ability to deliver a specific factor to a cell has proven to be a very effective therapeutic treatment, even so, if this does not occur in a regulated manner, it can be detrimental to the patient, especially in cases of random integration. Transgene expression seems at times to be unpredictable, with research showing that in some instances genetic variation can influence expression [66]. Depending on the status, the transgene will need to be expressed at unlike levels and potentially only in specific areas or cell types. To command the expression of transgenes and combat unpredictability, strategies such every bit the use of tissue-specific promoters and self-inactivation take been implemented. Tissue-specific promoters restrict the expression of the transgene to certain jail cell types only, thus limiting widespread expression. This is ideal when used therapeutically to target a specific cell or tissue type and avoid expression in non-target cells or tissues [67]. Furthermore, equally seen in the third-generation lentiviral vectors, a self-inactivating mechanism has been incorporated. Modification in the 3′ long concluding repeat prevents continued expression after one round of integration, effectively assuasive the amount of transgene expression to exist controlled with the dose of the vector [28]. Despite these positive outcomes, boosted enquiry that will enable tightly regulated transgene expression is still required.
Advertisement
5. Conclusions
Viral vector-based factor therapy has made very encouraging strides over the past two decades, suggesting in that location is a positive futurity for this therapy in medicine. Equally reported by IQVIA, the first one-half of 2021 saw a record amount invested into biopharmaceutical companies past venture capital firms, with cell and gene therapies attracting a significant amount of this investment [xi]. The value of pharmaceutical mergers and acquisitions (Grand&A) in 2021 showed a stark increase from the year before many of which were viral vector and factor therapy-based deals [xi, 68]. While these are promising statistics for the time to come of viral vector utilise, the concerns facing this method of cistron therapy still stand and will crave a considerable amount of research to overcome them. Moving forward, considering both the clinical trial data and the drawbacks of each viral vector, it seems lentiviral and adeno-associated viral vectors are the most favourable options to focus research on in the future. With express adverse reactions and favourable immunogenic profiles, these viral vectors have the potential to exist a key treatment in modernistic medicine.
Advertisement
Acknowledgments
A.Fifty.1000. Mahoney was supported by an Australian Government Research Grooming Stipend.
Advertizement
Conflict of interest
The authors declare no conflict of interest.
References
- ane.
Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, Gross F, Yvon East, Nusbaum P, et al. Gene therapy of human severe combined immunodeficiency (SCID)-X1 illness. Science. 2000; 288 :669-672. DOI: 10.1126/science.288.5466.669 - ii.
Acland GM, Aguirre GD, Ray J, Zhang Q, Aleman TS, Cideciyan AV, et al. Gene therapy restores vision in a canine model of childhood blindness. Nature Genetics. 2001; 28 :92-95. DOI: ten.1038/ng0501-92 - 3.
Nathwani AC, Reiss UM, Tuddenham EG, Rosales C, Chowdary P, McIntosh J, et al. Long-term safe and efficacy of factor Nine gene therapy in hemophilia B. New England Journal of Medicine. 2014; 371 :1994-2004. DOI: x.1056/NEJMoa1407309 - iv.
Ramamoorth M, Narvekar A. Non viral vectors in factor therapy-an overview. Journal of Clinical and Diagnostic Research: JCDR. 2015; 9 :GE01-GE06. DOI: 10.7860/JCDR/2015/10443.5394 - 5.
Wu P, Chen H, Jin R, Weng T, Ho JK, You lot C, et al. Non-viral gene commitment systems for tissue repair and regeneration. Journal of Translational Medicine. 2018; 16 :one-20. DOI: 10.1186/s12967-018-1402-1 - 6.
Wold WSM, Toth K. Adenovirus vectors for gene therapy, vaccination and cancer gene therapy. Current Gene Therapy. 2013; thirteen :421-433 - seven.
Zaiss A, Muruve D. Immunity to adeno-associated virus vectors in animals and humans: A continued challenge. Gene Therapy. 2008; 15 :808-816. DOI: 10.1038/gt.2008.54 - 8.
Kurian K, Watson C, Wyllie A. Retroviral vectors. Molecular Pathology. 2000; 53 :173. DOI: ten.1136/mp.53.4.173 - nine.
Buchschacher GL Jr, Wong-Staal F. Development of lentiviral vectors for cistron therapy for human diseases. Blood, The Journal of the American Society of Hematology. 2000; 95 :2499-2504. DOI: ten.1182/claret.V95.eight.2499 - 10.
Ginn SL, Amaya AK, Alexander IE, Edelstein M, Abedi MR. Gene therapy clinical trials worldwide to 2017: An update. The Journal of Gene Medicine. 2018; 20 :e3015. DOI: 10.1002/jgm.3015 - 11.
IQVIA. IQVIA Pharma Deals 2021 [Internet]. 2021. Available from: https://www.iqvia.com/library/white-papers/iqvia-pharma-deals-one-half-year-review-of-2021 [Accessed: 09 December 2021] - 12.
Bamford DH, Grimes JM, Stuart DI. What does construction tell united states about virus evolution? Current Stance in Structural Biology. 2005; 15 :655-663. DOI: ten.1016/j.sbi.2005.10.012 - 13.
Kay MA, Glorioso JC, Naldini L. Viral vectors for gene therapy: The fine art of turning infectious agents into vehicles of therapeutics. Nature Medicine. 2001; 7 :33-40. DOI: 10.1038/83324 - 14.
Raper SE, Chirmule N, Lee FS, Wivel NA, Bagg A, Gao Chiliad-p, et al. Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral factor transfer. Molecular Genetics and Metabolism. 2003; fourscore :148-158. DOI: ten.1016/j.ymgme.2003.08.016 - fifteen.
Hacein-Bey-Abina S, Von Kalle C, Schmidt M, McCormack Thousand, Wulffraat N, Leboulch PA, et al. LMO2-associated clonal T jail cell proliferation in two patients after gene therapy for SCID-X1. Science. 2003; 302 :415-419. DOI: 10.1126/science.1088547 - 16.
Kohn D, Mitsuya H, Ballow M, Selegue J, Barankiewicz J, Cohen A, et al. Institution and characterization of adenosine deaminase-deficient human being T cell lines. The Journal of Immunology. 1989; 142 :3971-3977 - 17.
Morgan RA, Anderson WF. Human gene therapy. Annual Review of Biochemistry. 1993; 62 :191-217. DOI: 10.1146/annurev.bi.62.070193.001203 - eighteen.
Randrianarison-Jewtoukoff 5, Perricaudet MJB. Recombinant adenoviruses as vaccines. Biologicals. 1995; 23 :145-157. DOI: 10.1006/biol.1995.0025 - 19.
Volpers C, Kochanek South. Adenoviral vectors for factor transfer and therapy. The Journal of Gene Medicine. 2004; six :S164-S171. DOI: x.1002/jgm.496 - 20.
Zhou HS, Liu DP, Liang CC. Challenges and strategies: The allowed responses in gene therapy. Medical Inquiry Reviews. 2004; 24 :748-761. DOI: 10.1002/med.20009 - 21.
Tazawa H, Kagawa Southward, Fujiwara T. Advances in adenovirus-mediated p53 cancer gene therapy. Adept Opinion on Biological Therapy. 2013; 13 :1569-1583. DOI: x.1517/14712598.2013.845662 - 22.
Xu R, Li H, Lai-yin T, Hsiang-fu K, Lu H, Lam K. Diabetes factor therapy: Potential and challenges. Electric current Gene Therapy. 2003; 3 :65-82. DOI: 10.2174/1566523033347444 - 23.
Worgall S, Crystal RG. Gene therapy. In: Lanza R, Langer R, Vacanti JP, Atala A, editors. Principles of Tissue Engineering. Cambridge, MA, United states: Academic Press; 2020. 34: 657-686. DOI: 10.1016/B978-0-12-398358-9.00034-3 - 24.
Hastie Eastward, Cataldi M, Marriott I, Grdzelishvili VZ. Agreement and altering cell tropism of vesicular stomatitis virus. Virus Enquiry. 2013; 176 :16-32 - 25.
O'Connor D. Introduction to gene and stem-jail cell therapy. In: Molecular and Cellular Therapies for Motor Neuron Diseases. Amsterdam, Netherlands: Elsevier; 2017. pp. 141-165. DOI: ten.1016/j.virusres.2013.06.003 - 26.
Ronen Yard, Negre O, Roth S, Colomb C, Malani N, Denaro M, et al. Distribution of lentiviral vector integration sites in mice following therapeutic factor transfer to treat β-thalassemia. Molecular Therapy. 2011; 19 :1273-1286. DOI: ten.1038/mt.2011.20 - 27.
Vannucci Fifty, Lai M, Chiuppesi F, Ceccherini-Nelli Fifty, Pistello M. Viral vectors: A look back and ahead on gene transfer technology. New Microbiologica. 2013; 36 :i-22 - 28.
Ho-hum T, Zufferey R, Kelly Thou, Mandel R, Nguyen K, Trono D, et al. A 3rd-generation lentivirus vector with a conditional packaging system. Periodical of Virology. 1998; 72 :8463-8471. DOI: 10.1128/JVI.72.eleven.8463-8471.1998 - 29.
Ma C-C, Wang Z-L, Xu T, He Z-Y, Wei Y-Q. The approved factor therapy drugs worldwide: From 1998 to 2019. Biotechnology Advances. 2020; 40 :107502. DOI: 10.1016/j.biotechadv.2019.107502 - 30.
Zabner J, Couture LA, Gregory RJ, Graham SM, Smith AE, Welsh MJ. Adenovirus-mediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosis. Prison cell. 1993; 75 :207-216. DOI: x.1016/0092-8674(93)80063-M - 31.
Zhang W-W, Li 50, Li D, Liu J, Li X, Li W, et al. The first approved gene therapy production for cancer Advertisement-p53 (Gendicine): 12 years in the clinic. Human Cistron Therapy. 2018; 29 :160-179. DOI: 10.1089/hum.2017.218 - 32.
Xia Y, Li X, Sun W. Applications of recombinant adenovirus-p53 gene therapy for cancers in the clinic in Communist china. Electric current Gene Therapy. 2020; xx :127-141. DOI: 10.2174/1566523220999200731003206 - 33.
Liang Yard. Oncorine, the globe starting time oncolytic virus medicine and its update in Prc. Electric current Cancer Drug Targets. 2018; 18 :171-176. DOI: 10.2174/1568009618666171129221503 - 34.
Wirth T, Parker Northward, Ylä-Herttuala South. History of gene therapy. Gene. 2013; 525 :162-169. DOI: 10.1016/j.gene.2013.03.137 - 35.
Atchison R, Casto BC, Hammon WM. Electron microscopy of adenovirus-associated virus (AAV) in jail cell cultures. Virology. 1996; 29 :353-357. DOI: 10.1016/0042-6822(66)90045-half dozen - 36.
Keeler AM, Flotte TR. Recombinant adeno-associated virus gene therapy in lite of Luxturna (and Zolgensma and Glybera): Where are we, and how did we become hither? Annual Review of Virology. 2019; half dozen :601-621. DOI: 10.1146/annurev-virology-092818-015530 - 37.
Gaudet D, Méthot J, Déry S, Brisson D, Essiembre C, Tremblay Yard, et al. Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPL S447X) gene therapy for lipoprotein lipase deficiency: An open up-label trial. Gene Therapy. 2013; 20 :361-369. DOI: 10.1038/gt.2012.43 - 38.
Russell Southward, Bennett J, Wellman JA, Chung DC, Yu Z-F, Tillman A, et al. Efficacy and prophylactic of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: A randomised, controlled, open-characterization, stage iii trial. The Lancet. 2017; 390 :849-860. DOI: 10.1016/S0140-6736(17)31868-8 - 39.
Bulaklak K, Gersbach CA. The once and future factor therapy. Nature Communications. 2020; eleven :1-4. DOI: ten.1038/s41467-020-19505-2 - 40.
Broekhoff TF, Sweegers CC, Krijkamp EM, Mantel-Teeuwisse AK, Leufkens HG, Goettsch WG, et al. Early on Cost-effectiveness of onasemnogene abeparvovec-xioi (zolgensma) and nusinersen (spinraza) treatment for spinal muscular atrophy i in the Netherlands with relapse scenarios. Value in Health. 2021; 24 :759-769. DOI: 10.1016/j.jval.2020.09.021 - 41.
McGarrity GJ, Hoyah G, Winemiller A, Andre K, Stein D, Blick G, et al. Patient monitoring and follow-up in lentiviral clinical trials. The Journal of Gene Medicine. 2013; 15 :78-82. DOI: 10.1002/jgm.2691 - 42.
Bach PB, Giralt SA, Saltz LB. FDA approval of tisagenlecleucel: Hope and complexities of a $475 000 cancer drug. Journal of the American Medical Association. 2017; 318 :1861-1862. DOI: ten.1001/jama.2017.15218 - 43.
Ali Due south, Kjeken R, Niederlaender C, Markey Thou, Saunders TS, Opsata Chiliad, et al. The European medicines agency review of Kymriah (Tisagenlecleucel) for the handling of astute lymphoblastic leukemia and diffuse large B-cell lymphoma. The Oncologist. 2020; 25 :e321-e327. DOI: 10.1634/theoncologist.2019-0233 - 44.
Chow VA, Shadman M, Gopal AK. Translating anti-CD19 Auto T-cell therapy into clinical practice for relapsed/refractory lengthened big B-cell lymphoma. Blood Spotlight. 2018; 132 :777-781. DOI: 10.1182/blood-2018-04-839217 - 45.
The Journal of Cistron Medicine. Gene Therapy Clinical Trials Worldwide [Internet]. 2021. Bachelor from: https://a873679.fmphost.com/fmi/webd/GTCT [Accessed: 03 November 2021] - 46.
Stirnadel-Farrant H, Kudari 1000, Garman Due north, Imrie J, Chopra B, Giannelli S, et al. Gene therapy in rare diseases: The benefits and challenges of developing a patient-centric registry for Strimvelis in ADA-SCID. Orphanet Periodical of Rare Diseases. 2018; 13 :ane-10. DOI: ten.1186/s13023-018-0791-9 - 47.
Shaw AR, Suzuki Yard. Immunology of adenoviral vectors in cancer therapy. Molecular Therapy-Methods & Clinical Development. 2019; 15 :418-429. DOI: 10.1016/j.omtm.2019.11.001 - 48.
Mueller C, Gernoux G, Gruntman AM, Borel F, Reeves EP, Calcedo R, et al. 5 year expression and neutrophil defect repair afterward gene therapy in blastoff-one antitrypsin deficiency. Molecular Therapy. 2017; 25 :1387-1394. DOI: 10.1016/j.ymthe.2017.03.029 - 49.
Bennett J, Wellman J, Marshall KA, McCague S, Ashtari Thou, DiStefano-Pappas J, et al. Safety and immovability of effect of contralateral-eye assistants of AAV2 gene therapy in patients with childhood-onset incomprehension caused by RPE65 mutations: A follow-on phase 1 trial. The Lancet. 2016; 388 :661-672. DOI: ten.1016/S0140-6736(16)30371-3 - 50.
George LA, Sullivan SK, Giermasz A, Rasko JE, Samelson-Jones BJ, Ducore J, et al. Hemophilia B gene therapy with a high-specific-activity factor IX variant. New England Journal of Medicine. 2017; 377 :2215-2227. DOI: 10.1056/NEJMoa1708538 - 51.
George LA, Ragni MV, Samelson-Jones BJ, Cuker A, Runoski AR, Cole Chiliad, et al. Spk-8011: Preliminary results from a phase 1/2 dose escalation trial of an investigational AAV-mediated cistron therapy for hemophilia A. Blood. 2017; 130 :604. DOI: x.1182/claret.V130.Suppl_1.604.604 - 52.
Milone MC, O'Doherty U. Clinical use of lentiviral vectors. Leukemia. 2018; 32 :1529-1541. DOI: 10.1038/s41375-018-0106-0 - 53.
Zufferey R, Dull T, Mandel RJ, Bukovsky A, Quiroz D, Naldini L, et al. Cocky-inactivating lentivirus vector for prophylactic and efficient in vivo factor delivery. Journal of Virology. 1998; 72 :9873-9880. DOI: ten.1128/JVI.72.12.9873-9880.1998 - 54.
Bouwman W, Verhaegh W, Holtzer L, van de Stolpe A. Measurement of cellular immune response to viral infection and vaccination. Frontiers in Immunology. 2020; 11 :2719. DOI: 10.3389/fimmu.2020.575074 - 55.
Huang X, Yang Y. Innate immune recognition of viruses and viral vectors. Human being Gene Therapy. 2009; twenty :293-301. DOI: 10.1089/hum.2008.141 - 56.
Lynch JP 3, Kajon AE. Adenovirus: Epidemiology, global spread of novel serotypes, and advances in treatment and prevention. Seminars in Respiratory and Critical Care Medicine, Thieme Medical Publishers. 2016; 37 :586-602. DOI: 10.1055/s-0036-1584923 - 57.
M.J. Imperiale, Keeping adenovirus away from the liver, Cell Host & Microbe. 2008;3:119-120. DOI: doi.org/10.1016/j.chom.2008.02.007 - 58.
Calcedo R, Vandenberghe LH, Gao G, Lin J, Wilson JM. Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. The Journal of Infectious Diseases. 2009; 199 :381-390. DOI: ten.1086/595830 - 59.
Bartlett DL, Liu Z, Sathaiah G, Ravindranathan R, Guo Z, He Y, et al. Oncolytic viruses every bit therapeutic cancer vaccines. Molecular Cancer. 2013; 12 :i-16. DOI: 10.1186/1476-4598-12-103 - 60.
Buffa V, Negri DR, Leone P, Borghi Grand, Bona R, Michelini Z, et al. Evaluation of a self-inactivating lentiviral vector expressing simian immunodeficiency virus gag for induction of specific immune responses in vitro and in vivo. Viral Immunology. 2006; nineteen :690-701. DOI: x.1089/vim.2006.19.690 - 61.
Kallel H, Kamen AA. Large-scale adenovirus and poxvirus-vectored vaccine manufacturing to enable clinical trials. Biotechnology Journal. 2015; 10 :741-747. DOI: 10.1002/biot.201400390 - 62.
Nascimento I, Leite L. Recombinant vaccines and the development of new vaccine strategies. Brazilian Journal of Medical and Biological Inquiry. 2012; 45 :102-1111. DOI: 10.1590/S0100-879X2012007500142 - 63.
Merten O-W, Schweizer 1000, Chahal P, Kamen AA. Manufacturing of viral vectors for factor therapy: Role I. Upstream processing. Pharmaceutical Bioprocessing. 2014; two :183-203. DOI: 10.4155/pbp.14.16 - 64.
Chen Thousand-D, Wu X-X, Yu D-S, Ou H-L, Li Y-H, Zhou Y-Q, et al. Procedure optimization for the rapid product of adenoviral vectors for clinical trials in a dispensable bioreactor arrangement. Applied Microbiology and Biotechnology. 2018; 102 :6469-6477. DOI: 10.1007/s00253-018-9091-five - 65.
Sharon D, Kamen A. Advancements in the design and scalable production of viral gene transfer vectors. Biotechnology and Bioengineering. 2018; 115 :25-40. DOI: x.1002/chip.26461 - 66.
Suwanmanee T, Ferris MT, Hu P, Gui T, Montgomery SA, de Villena FP-One thousand, et al. Toward personalized gene therapy: Characterizing the host genetic control of lentiviral-vector-mediated hepatic gene commitment. Molecular Therapy-Methods & Clinical Development. 2017; five :83-92. DOI: 10.1016/j.omtm.2017.03.009 - 67.
Zheng C, Baum BJ. Evaluation of promoters for use in tissue-specific gene delivery. Gene Therapy Protocols. 2008; 434 :205-219. DOI: 10.1007/978-ane-60327-248-3_13 - 68.
Biopharmaceutical Dealmakers & DealForma, M&As make their mark [Cyberspace]. 2020. Available from: https://world wide web.nature.com/articles/d43747-020-00841-vii [Accessed: x Decemeber 2021]
Submitted: Dec 22nd, 2021 Reviewed: January 10th, 2022 Published: March 31st, 2022
© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed nether the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Source: https://www.intechopen.com/online-first/80374
0 Response to "Viral Vectors for Gene Therapy the Art of Turning Infectious Agents Into Vehicles of Therapeutics"
Post a Comment