The Platform Vector Gene Therapies Project: Increasing the Efficiency of Adeno-Associated Virus Gene Therapy Clinical Trial Startup

Brooks, Philip J.; Ottinger, Elizabeth A.; Portero, Deanna; Lomash, Richa Madan; Alimardanov, Asaf; Terse, Pramod; Xu, Xin; Chandler, Randy J.; Hauserman, Janelle Geist; Esposito, Eric; Bönnemann, Carsten G.; Venditti, Charles P.; Austin, Christopher P.; Pariser, Anne; Lo, Donald C.; Averion, Gilberto V.; Balakrishnan, Krishna; Burden, Steven; Campbell, Eggerton; Chen, Catherine; Driscoll, Claire; Dukhanina, Oksana I.; Ferry, Susan; Foley, Alicia; Li, Lina; Manoli, Irini; Mendoza, Christopher; Oury, J.-F.; Porter, Forbes D.; Portilla, Lili; Saade, D.; Shchelochkov, Oleg A.; Sloan, Jennifer L.; Todd, Joshua J.; Toney, London; Ryzin, Carol Van; Vepa, Sury; Wagner, E.; Wang, Amy

doi:10.1089/hum.2020.259

Cited by 22 publications

(20 citation statements)

References 25 publications

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“…AAVs are a class of viruses in the Parvovirus family that can infect both dividing and non-dividing cells in humans, but they are not believed to cause disease [ 24 , 25 , 26 ]. This lack of pathogenicity, combined with a relatively small genome of 4.8 kilobases, has made AAV an attractive option for viral gene therapy, and hundreds of AAV-based therapies have undergone or are currently undergoing clinical trials [ 24 , 27 , 28 ]. AAV is a simple structure containing the viral ssDNA genome enclosed in a protein capsid, which plays important roles in protection, cell membrane permeation, and cellular targeting [ 29 ].…”

Section: Exon 2 Skipping For Exon 2 Duplication—astellas Gene Therapiesmentioning

confidence: 99%

Antisense and Gene Therapy Options for Duchenne Muscular Dystrophy Arising from Mutations in the N-Terminal Hotspot

Wilton-Clark

Yokota

2022

Genes

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Duchenne muscular dystrophy (DMD) is a fatal genetic disease affecting children that is caused by a mutation in the gene encoding for dystrophin. In the absence of functional dystrophin, patients experience progressive muscle deterioration, leaving them wheelchair-bound by age 12 and with few patients surviving beyond their third decade of life as the disease advances and causes cardiac and respiratory difficulties. In recent years, an increasing number of antisense and gene therapies have been studied for the treatment of muscular dystrophy; however, few of these therapies focus on treating mutations arising in the N-terminal encoding region of the dystrophin gene. This review summarizes the current state of development of N-terminal antisense and gene therapies for DMD, mainly focusing on exon-skipping therapy for duplications and deletions, as well as microdystrophin therapy.

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Section: Exon 2 Skipping For Exon 2 Duplication—astellas Gene Therapiesmentioning

confidence: 99%

Antisense and Gene Therapy Options for Duchenne Muscular Dystrophy Arising from Mutations in the N-Terminal Hotspot

Wilton-Clark

Yokota

2022

Genes

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“…Xu et al, recently designed an OAd encoding a soluble TGFβ receptor II fused with a human IgG Fc fragment (sTGFβRIIFc), which is a TGFβ decoy that inhibits TGFβ signaling. In immunocompetent mouse models of breast and renal cancers, addition of the sTGFβRIIFc-expressing OAd significantly augmented anti-PD-1 and anti-CTLA-4-mediated inhibition of tumor metastasis [ 132 ]. In addition to the aforementioned ICB proteins, other ICB proteins are also considered as therapeutic targets.…”

Section: Ovs In Combination With Immunotherapymentioning

confidence: 99%

Oncolytic virotherapy reverses the immunosuppressive tumor microenvironment and its potential in combination with immunotherapy

Zhang

Chen

et al. 2021

Cancer Cell Int

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It has been intensively reported that the immunosuppressive tumor microenvironment (TME) results in tumor resistance to immunotherapy, especially immune checkpoint blockade and chimeric T cell antigen therapy. As an emerging therapeutic agent, oncolytic viruses (OVs) can specifically kill malignant cells and modify immune and non-immune TME components through their intrinsic properties or genetically incorporated with TME regulators. Strategies of manipulating OVs against the immunosuppressive TME include serving as a cancer vaccine, expressing proinflammatory factors and immune checkpoint inhibitors, and regulating nonimmune stromal constituents. In this review, we summarized the mechanisms and applications of OVs against the immunosuppressive TME, and strategies of OVs in combination with immunotherapy. We also introduced future directions to achieve efficient clinical translation including optimization of preclinical models that simulate the human TME and achieving systemic delivery of OVs.

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“…Such an approach ultimately streamlines review by regulatory authorities of applications by sponsors, and there is a greater need for more common and customizable tools, reagents, and vectors for the modular, programmable platforms used in vaccines and CGT biomanufacturing (see Figure 1). Eff orts like Platform Vector Gene Therapy [6], Coalition for Epidemic Preparedness Innovations' (CEPI) platform technologies for Disease X, and proprietary platforms at Moderna [8] provide some examples, and further integration of technology, best-practices, and standardization eff orts across both CGT and vaccine product development is possible.…”

Section: Customizable Platformsmentioning

confidence: 99%

“…Even before the COVID-19 pandemic, high demand and short supply were common features of next-generation CGTs and vaccines. For example, there were year-long queues at biomanufacturing facilities to make clinical-grade viral vectors from 2017 onwards [6]. The active ingredients in many CGTs also contain RNAs, proteins, and viral vectors, as in vaccines (see Figure 1).…”

mentioning

confidence: 99%

Integrating United States Biomanufacturing Across Vaccines and Therapeutics

Saha

Roy

2021

NAM Perspectives

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The Platform Vector Gene Therapies Project: Increasing the Efficiency of Adeno-Associated Virus Gene Therapy Clinical Trial Startup

Cited by 22 publications

References 25 publications

Antisense and Gene Therapy Options for Duchenne Muscular Dystrophy Arising from Mutations in the N-Terminal Hotspot

Antisense and Gene Therapy Options for Duchenne Muscular Dystrophy Arising from Mutations in the N-Terminal Hotspot

Oncolytic virotherapy reverses the immunosuppressive tumor microenvironment and its potential in combination with immunotherapy

Integrating United States Biomanufacturing Across Vaccines and Therapeutics

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