Coevolution of Adeno-associated Virus Capsid Antigenicity and Tropism through a Structure-Guided Approach
L. Patrick Havlik, Katherine E. Simon, J. Kennon Smith, Kelli A. Klinc, Longping V. Tse, Daniel K. Oh, Marco M. Fanous, Rita M. Meganck, Mario Mietzsch, Jürgen A. Kleinschmidt, Mavis Agbandje‐McKenna, Aravind Asokan
Abstract
Clinical gene therapy with recombinant AAV vectors has largely relied on natural capsid isolates. There is an unmet need to comprehensively improve AAV tissue tropism, transduction efficiency, and antibody evasion. Such cannot be achieved by utilizing capsid sequence data alone but requires harnessing the 3D structural properties of AAV capsids. Here, we combine rational design and library-based evolution to coevolve multiple, desirable properties onto AAV by harnessing 3D structural information.
Topics & Concepts
CapsidBiologyTropismVirologyAntigenicityTransduction (biophysics)Tissue tropismAdeno-associated virusRecombinant DNAComputational biologyVirusGeneGeneticsAntibodyVector (molecular biology)BiochemistryVirus-based gene therapy researchCRISPR and Genetic EngineeringViral Infectious Diseases and Gene Expression in Insects