Advances in recombinant adeno-associated viral vectors for gene delivery.
Recombinant adeno-associated viral vectors (rAAV) have now been used in several clinical trials to treat a variety of diseases, and are currently the preferred choice of many investigators in the field, due to both their low pathogenicity and immunogenicity compared with other viral vectors, as well as localized long-term gene expression, despite their limitations of DNA size packaging and speed of expression. Recently, a number of advances have led to new generations of rAAV vectors, with improved features. This review addresses the various strategies employed to such effect, namely exploring distinct serotype tropisms, the production of mosaic and chimeric capsids, the selection of vectors through directed evolution, the development of self-complementary vectors, the use of pharmacological adjuvants and the induction of specific capsid mutations. Such approaches are expected to help the establishment of rAAV-based clinical gene therapy in the near future.
Hilda
H
Petrs-Silva
Laboratório de Neurogênese, Centro de Ciências da Súde, bloco G, Cidade Universitária, 21941-902, Rio de Janeiro, Brazil. rlinden@biof.ufrj.br.
Rafael
R
Linden
D000595:Amino Acid Sequence; D000818:Animals; D036022:Capsid Proteins / Q000235:genetics; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D036022:Capsid Proteins; D011994:Recombinant Proteins