Adeno-associated Virus (AAV) Capsid Chimeras with Enhanced Infectivity Reveal a Core Element in the AAV Genome Critical for both Cell Transduction and Capsid Assembly
Lydia Viney, Tilmann Bürckstümmer, Courtnee Eddington, Mario Mietzsch, Modassir Choudhry, Tom Henley, Mavis Agbandje‐McKenna
Abstract
gene delivery has been high, which has resulted in unfortunate recent safety concerns and deaths in patients given higher-dose AAV gene therapy. We have generated new AAV variants possessing unique combinations of capsid proteins for gene and cell therapy applications termed AAV-XV, which have high levels of cell transduction and gene delivery at lower MOI. Furthermore, we demonstrate a novel finding, and an important consideration for recombinant AAV design, that a region of the AAV genome encoding the capsid viral protein and AAP is critical for both virus yield and the enhancement of infection/transduction.
Topics & Concepts
CapsidAdeno-associated virusBiologyTransduction (biophysics)Genetic enhancementVirologyGene deliveryVirusTransgeneInfectivityGeneGeneticsVector (molecular biology)Recombinant DNABiochemistryVirus-based gene therapy researchCRISPR and Genetic EngineeringViral Infectious Diseases and Gene Expression in Insects