Adeno-associated viral (AAV) vectors are showing great promise in gene therapy as evidenced by several recent FDA (U.S. Food and Drug Administration) and EMA (European Medicines Agency) approvals for treatments in rare diseases. AAV is a single-stranded DNA virus that is non-pathogenic to humans, has high transduction efficiency, and is unable to replicate itself. Recombinant AAV (rAAV) used in the clinic can either stably express gene products from unintegrated episomes in quiescent tissues, or via targeted integration in actively dividing tissues when designed with appropriate homology arms. Nearly 200 rAAV clinical trials for various indications have been performed, and countless investigational new drug applications are in various stages of review at the FDA and EMA.
While historically thought of as a ‘non-immunogenic’ virus in humans, several recent high-profile severe adverse events using high-dose rAAV systemically have renewed the urgency to further understand the immune response to this powerful vector. While it remains the gold-standard for safety, a more nuanced look at emerging science and technology developments in this space is warranted.
Thus, we welcome submission of the following types of articles: Original Research, Methods, Systematic Review, Review, Mini-Review, Hypothesis and Theory, Perspective, Clinical Trial, and Case Report in the following areas:
- Pre-existing and innate immunities to rAAVs and their impact on rAAV-based gene therapeutics.
- Immune responses to capsids or transgene products: basic biology or technology developments.
- Immunomodulatory agents to facilitate the safer use of rAAV in patients.
- Novel vector design components to improve safety: capsids, promoters and regulatory elements to detarget from immune cells, etc.
- Improved AAV delivery methods beyond systemic administration for targeted delivery.
- Methods to better assess pre-existing neutralizing antibody levels and overcome this immunological barrier to rAAV gene delivery.
- Preclinical or clinical data on biomarkers of AAV toxicity or undesired immune responses.
- Novel manufacturing/purification methodologies to reduce impurity burdens in vector lots.
- Fundamental basic biology of AAV relevant to both innate and adaptive immune responses to vector.
- Innovative preclinical animal models to better assess biodistribution, toxicity, dosing regimens.
- rAAV-based delivery of immunotherapeutics: challenges and strategies to overcome.
- rAAV-based immunotherapeutics: translation in primates.
Dr. Gao is the co-founder of Voyager Therapeutics, Adrenas Therapeutics and Aspa Therapeutics. His research laboratory receives financial support from sponsored research agreements with various companies including Merck and LuYe Pharma. The other Topic Editors declare no conflict of interest with regards to the Research Topic theme
Adeno-associated viral (AAV) vectors are showing great promise in gene therapy as evidenced by several recent FDA (U.S. Food and Drug Administration) and EMA (European Medicines Agency) approvals for treatments in rare diseases. AAV is a single-stranded DNA virus that is non-pathogenic to humans, has high transduction efficiency, and is unable to replicate itself. Recombinant AAV (rAAV) used in the clinic can either stably express gene products from unintegrated episomes in quiescent tissues, or via targeted integration in actively dividing tissues when designed with appropriate homology arms. Nearly 200 rAAV clinical trials for various indications have been performed, and countless investigational new drug applications are in various stages of review at the FDA and EMA.
While historically thought of as a ‘non-immunogenic’ virus in humans, several recent high-profile severe adverse events using high-dose rAAV systemically have renewed the urgency to further understand the immune response to this powerful vector. While it remains the gold-standard for safety, a more nuanced look at emerging science and technology developments in this space is warranted.
Thus, we welcome submission of the following types of articles: Original Research, Methods, Systematic Review, Review, Mini-Review, Hypothesis and Theory, Perspective, Clinical Trial, and Case Report in the following areas:
- Pre-existing and innate immunities to rAAVs and their impact on rAAV-based gene therapeutics.
- Immune responses to capsids or transgene products: basic biology or technology developments.
- Immunomodulatory agents to facilitate the safer use of rAAV in patients.
- Novel vector design components to improve safety: capsids, promoters and regulatory elements to detarget from immune cells, etc.
- Improved AAV delivery methods beyond systemic administration for targeted delivery.
- Methods to better assess pre-existing neutralizing antibody levels and overcome this immunological barrier to rAAV gene delivery.
- Preclinical or clinical data on biomarkers of AAV toxicity or undesired immune responses.
- Novel manufacturing/purification methodologies to reduce impurity burdens in vector lots.
- Fundamental basic biology of AAV relevant to both innate and adaptive immune responses to vector.
- Innovative preclinical animal models to better assess biodistribution, toxicity, dosing regimens.
- rAAV-based delivery of immunotherapeutics: challenges and strategies to overcome.
- rAAV-based immunotherapeutics: translation in primates.
Dr. Gao is the co-founder of Voyager Therapeutics, Adrenas Therapeutics and Aspa Therapeutics. His research laboratory receives financial support from sponsored research agreements with various companies including Merck and LuYe Pharma. The other Topic Editors declare no conflict of interest with regards to the Research Topic theme