Liver induced transgene tolerance with AAV vectors
Open accessAbstract
Immune tolerance is a vital component of immunity, as persistent activation of immune cells causes significant tissue damage and loss of tolerance leads to autoimmunity. Likewise, unwanted immune responses can occur in inherited disorders, such as hemophilia and Pompe disease, in which patients lack any expression of protein, during treatment with enzyme replacement therapy, or gene therapy. While the liver has long been known as being tolerogenic, it was only recently appreciated in the last decade that liver directed adeno-associated virus (AAV) gene therapy can induce systemic tolerance to a transgene. In this review, we look at the mechanisms behind liver induced tolerance, discuss different factors influencing successful tolerance induction with AAV, and applications where AAV mediated tolerance may be helpful.
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Mouse studies have shown liver-directed AAV gene therapy results in tolerogenic responses by the induction of Tregs.
“mouse studies have shown liver-directed AAV gene therapy results in tolerogenic responses by the induction of Tregs,52, 53, 54, 55, 56, 57, 58, 59”
From Modulating immune responses to AAV by expanded polyclonal T-regs and capsid specific chimeric antigen receptor T-regulatory cells (2021) · cites this paper as [52]
Regulatory T cells (Treg) modulate immune tolerance towards transgene product and capsid that are vital to durable expression of therapeutic protein.
“Regulatory T cells (Treg) modulate immune tolerance towards transgene product and capsid that are vital to durable expression of therapeutic protein (16, 17).”
From Immunomodulation in Administration of RAAV: Preclinical and Clinical Adjuvant Pharmacotherapies (2021) · cites this paper as [16]
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References 171 · Cited by 81
Research works printed but not linked: 1
- [163]Uretsky S Sahel J Galy A Thomasson N Honnet G A recombinant AAV2/2 carrying the wild-type ND4 gene for the treatment of LHON: preliminary results of a first-in-man study and upcoming pivotal efficacy trials 12th International Symposium on Ocular Pharmacology and Therapeutics Berlin 2016
- Authors
- Keeler, G. D., Markusic, D. M., & Hoffman, B. E.
- Affiliations
- University of Florida (US)
- Corresponding author
- Hoffman, Brad E.
- Venue
- Cellular Immunology
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 342
- Pages
- 103728
- ISSN
- 0008-8749 (ISSN-L)
- PMC
- PMC5988960
- OpenAlex
- W2775750859
- Cited by
- 81
- References
- 171
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 8 · 2023: 11 · 2022: 7 · 2021: 11 · 2020: 8 · 2019: 7 · 2018: 3
- FWCI
- 0.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cellular Immunology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Multiple Sclerosis Society (PP2157, RG 5315-A-1)
- NIH-NIAID (R01AI128074)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- immune tolerance, adeno-associated virus vectors, liver-directed gene therapy, autoimmunity, enzyme replacement therapy, hemophilia, Pompe disease, gene therapy
- MeSH terms
- Dependovirus, Autoimmune Diseases, Dendritic Cells, Genetic Vectors, Humans, Immune Tolerance, Liver, Genetic Therapy, Transgenes, T-Lymphocytes, Regulatory
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