AAV Immunotoxicity: Implications in Anti-HBV Gene Therapy

Autor: Ridhwaanah Jacobs, Makafui Dennis Dogbey, Njabulo Mnyandu, Keila Neves, Stefan Barth, Patrick Arbuthnot, Mohube Betty Maepa
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Microorganisms, Vol 11, Iss 12, p 2985 (2023)
Druh dokumentu: article
ISSN: 2076-2607
DOI: 10.3390/microorganisms11122985
Popis: Hepatitis B virus (HBV) has afflicted humankind for decades and there is still no treatment that can clear the infection. The development of recombinant adeno-associated virus (rAAV)-based gene therapy for HBV infection has become important in recent years and research has made exciting leaps. Initial studies, mainly using mouse models, showed that rAAVs are non-toxic and induce minimal immune responses. However, several later studies demonstrated rAAV toxicity, which is inextricably associated with immunogenicity. This is a major setback for the progression of rAAV-based therapies toward clinical application. Research aimed at understanding the mechanisms behind rAAV immunity and toxicity has contributed significantly to the inception of approaches to overcoming these challenges. The target tissue, the features of the vector, and the vector dose are some of the determinants of AAV toxicity, with the latter being associated with the most severe adverse events. This review discusses our current understanding of rAAV immunogenicity, toxicity, and approaches to overcoming these hurdles. How this information and current knowledge about HBV biology and immunity can be harnessed in the efforts to design safe and effective anti-HBV rAAVs is discussed.
Databáze: Directory of Open Access Journals