Engineering adeno-associated viruses for clinical gene therapy

Nat Rev Genet. 2014 Jul;15(7):445-51. doi: 10.1038/nrg3742. Epub 2014 May 20.


Clinical gene therapy has been increasingly successful owing both to an enhanced molecular understanding of human disease and to progressively improving gene delivery technologies. Among these technologies, delivery vectors based on adeno-associated viruses (AAVs) have emerged as safe and effective and, in one recent case, have led to regulatory approval. Although shortcomings in viral vector properties will render extension of such successes to many other human diseases challenging, new approaches to engineer and improve AAV vectors and their genetic cargo are increasingly helping to overcome these barriers.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Capsid / chemistry
  • Capsid / metabolism
  • Clinical Trials as Topic
  • DNA, Viral / genetics*
  • Dependovirus / genetics*
  • Directed Molecular Evolution
  • Genetic Engineering*
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Genome, Viral*
  • Hemophilia A / genetics
  • Hemophilia A / pathology
  • Hemophilia A / therapy
  • Humans
  • Metabolic Diseases / genetics
  • Metabolic Diseases / pathology
  • Metabolic Diseases / therapy
  • Muscular Dystrophies / genetics
  • Muscular Dystrophies / pathology
  • Muscular Dystrophies / therapy
  • Viral Proteins / genetics*


  • DNA, Viral
  • Viral Proteins