Premium
Comparison of the transduction efficiency of tyrosine‐mutant adeno‐associated virus serotype vectors in kidney
Author(s) -
Qi Yan F.,
Li Qiu H.,
Shenoy Vinayak,
Zingler Michael,
Jun Joo Y.,
Verma Amrisha,
Katovich Michael J.,
Raizada Mohan K.
Publication year - 2013
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12037
Subject(s) - microinjection , adeno associated virus , transduction (biophysics) , mutant , green fluorescent protein , genetic enhancement , kidney , biology , microbiology and biotechnology , virology , reporter gene , viral vector , gene , vector (molecular biology) , gene expression , genetics , recombinant dna , biochemistry
Summary Gene therapy has a distinct potential to treat kidney diseases. However, the efficient transduction of a significant number of renal cells by viral vectors has been difficult to accomplish. Previous studies indicate that adeno‐associated virus ( AAV ) can transduce renal cells with variable and suboptimal efficiency. Because new and innovative mutants of AAV are now available, we compared their efficacy in transducing rat kidneys. We compared five types of AAV mutants ( AAV 2 mut‐triple, AAV 2 sextuple, AAV 8 mut447, AAV 8 mut733 and AAV 9 mut446) carrying a green fluorescence protein ( GFP ) reporter gene. A pressure microinjection technique was used to inject either 1.5 × 10 11 vector genome (vg) AAV mutants or three dose of AAV 2 sextuple into the renal cortex of rats. The microinjection approach has not been used in AAV ‐mediated renal gene transfer thus far. Slow and sustained microinjection enables continuous administration of the viral vector to the kidney cortex and limits any damage to the kidney, because the tip of a glass micropipette is very small. Three weeks after injection, the kidneys were collected and evaluated for GFP expression. Among the various mutated AAV serotypes studied, only AAV 2 sextuple showed robust GFP expression in renal tissue. The AAV 2 sextuple serotype appears to be an efficient gene transfer vector to preferentially target renal tubular epithelial cells. A combination of the AAV 2 sextuple and the microinjection technique holds the key to the future of therapeutic treatments for kidney diseases.