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Redirecting AAV vectors to extrahepatic tissues

Aravind Asokan, Shen Shen

2023Molecular Therapy34 citationsDOIOpen Access PDF

Abstract

Recombinant adeno-associated viral (AAV) vectors are the current benchmark for systemic delivery of gene therapies to multiple organs in vivo. Despite clinical successes, safe and effective gene delivery to extrahepatic tissues has proven challenging due to dose limiting toxicity arising from high liver uptake of AAV vectors. Deeper understanding of AAV structure, receptor biology, and pharmacology has enabled the design and engineering of liver-de-targeted capsids ushering in several new vector candidates. This next generation of AAVs offers significant promise for extrahepatic gene delivery to cardiovascular, musculoskeletal, and neurological tissues with improved safety profiles.

Topics & Concepts

Vector (molecular biology)Gene deliveryGenetic enhancementLimitingCapsidAdeno-associated virusBiologyViral vectorRecombinant DNAComputational biologyGeneBioinformaticsMedicineVirologyVirusGeneticsEngineeringMechanical engineeringVirus-based gene therapy researchRNA Interference and Gene DeliveryViral Infectious Diseases and Gene Expression in Insects