Engineering AAV receptor footprints for gene therapy.
Adeno-associated viruses (AAV) are currently at the forefront of human gene therapy clinical trials as recombinant vectors. Significant progress has been made in elucidating the structure, biology and tropisms of different naturally occurring AAV isolates in the past decade. In particular, a spectrum of AAV capsid interactions with host receptors have been identified and characterized. These studies have enabled a better understanding of key determinants of AAV cell recognition and entry in different hosts. This knowledge is now being applied toward engineering new, lab-derived AAV capsids with favorable transduction profiles. The current review conveys a structural perspective of capsid-glycan interactions and provides a roadmap for generating synthetic strains by engineering AAV receptor footprints.
Gene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Victoria J
VJ
Madigan
Gene Therapy Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Department of Biochemistry & Biophysics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. Electronic address: aravind@med.unc.edu.
Aravind
A
Asokan
D002213:Capsid / Q000737:chemistry; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000229:Dependovirus / Q000235:genetics* / Q000502:physiology*; D005818:Genetic Engineering / Q000379:methods*; D015316:Genetic Therapy; D005822:Genetic Vectors; D054884:Host-Pathogen Interactions; D006801:Humans; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics* / Q000378:metabolism*
D036022:Capsid Proteins; D011134:Polysaccharides; D011991:Receptors, Virus