Viruses, Vol. 16, Pages 442: Natural Adeno-Associated Virus Serotypes and Engineered Adeno-Associated Virus Capsid Variants: Tropism Differences and Mechanistic Insights
Viruses, Vol. 16, Pages 442: Natural Adeno-Associated Virus Serotypes and Engineered Adeno-Associated Virus Capsid Variants: Tropism Differences and Mechanistic Insights
Viruses doi: 10.3390/v16030442
Authors:
Estrella Lopez-Gordo
Kyle Chamberlain
Jalish Mahmud Riyad
Erik Kohlbrenner
Thomas Weber
Today, adeno-associated virus (AAV)-based vectors are arguably the most promising in vivo gene delivery vehicles for durable therapeutic gene expression. Advances in molecular engineering, high-throughput screening platforms, and computational techniques have resulted in a toolbox of capsid variants with enhanced performance over parental serotypes. Despite their considerable promise and emerging clinical success, there are still obstacles hindering their broader use, including limited transduction capabilities, tissue/cell type-specific tropism and penetration into tissues through anatomical barriers, off-target tissue biodistribution, intracellular degradation, immune recognition, and a lack of translatability from preclinical models to clinical settings. Here, we first describe the transduction mechanisms of natural AAV serotypes and explore the current understanding of the systemic and cellular hurdles to efficient transduction. We then outline progress in developing designer AAV capsid variants, highlighting the seminal discoveries of variants which can transduce the central nervous system upon systemic administration, and, to a lesser extent, discuss the targeti...
Source: Viruses - Category: Virology Authors: Estrella Lopez-Gordo Kyle Chamberlain Jalish Mahmud Riyad Erik Kohlbrenner Thomas Weber Tags: Review Source Type: research