Receptor targeting of adeno-associated virus vectors

Abstract

Adeno-associated virus (AAV) is a promising vector for human somatic gene therapy. However, its broad host range is a disadvantage for in vivo gene therapy, because it does not allow the selective tissue-or organ-restricted transduction required to enhance the safety and efficiency of the gene transfer. Therefore, increasing efforts are being made to target AAV-2-based vectors to specific receptors. The studies summarized in this review show that it is possible to target AAV-2 to a specific cell. So far, the most promising approach is the genetic modification of the viral capsid. However, the currently available AAV-2 targeting vectors need to be improved with regard to the elimination of the wild-type AAV-2 tropism and the improvement of infectious titers. The creation of highly efficient AAV-2 targeting vectors will also require a better understanding of the transmembrane and intracellular processing of this virus.

Chromatographic purification of recombinant adenoviral and adeno-associated viral vectors: methods and implications

“…Targeting of several cell-specific receptors by inserting corresponding ligands into the virus capsid proteins resulted in the enhancement of cell transduction efficiency. 84,85 Pseudotyping rAAV vector, that is, using an alternative serotype capsid to package the rAAV vector genome, can also substantially increase the vector transduction efficiency and broaden the host range for rAAV-mediated gene transfer (reviewed by Flotte). 9 Utilization of emerging alternative serotypes and receptor targeted capsid mutants demands the developPurification of adenoviral and AAV vectors E Burova and E Ioffe ment of efficient methods for their production and purification.…”

Heart-targeted adeno-associated viral vectors selected by in vivo biopanning of a random viral display peptide library

“…So far, cell receptor-directed targeting and expression targeting are the most successfully applied techniques. [1][2][3][4][5][6] Capsids of adeno-associated virus (AAV)-derived vectors have been modified for receptor targeting basically in three ways: (1) by conjugating receptorbinding ligands to their capsids, (2) by genetic insertion of ligands into the capsid (for reviews see Muzyczka and Warrington 1 and Buning et al 7 ) and (3) by DNA shuffling from different AAV serotypes. [8][9][10] Pseudotyping of AAV vectors with capsids of different serotypes also expanded the range of infectable cells, 11 but has not resulted in cell type-selective transduction after systemic application.…”

Intracellular trafficking of adeno-associated viral vectors

“…15,16 These AAV serotypes share a common genome structure, but have varying abilities to infect different cell types and tissue based on their capsid protein recognition by cell surface receptors. The repertoire of rAAV vectors has also been greatly expanded by the development of technologies to pseudo-package rAAV genomes, [17][18][19][20] package AAV genomes with two different ITR serotypes, 21 generate mosaic rAAV particles with more than one capsid serotype, [22][23][24] retarget AAV by generating rAAV capsid modification [25][26][27][28][29] and generate rAAV with chemically modified capsids. 30 These technologies have greatly expanded the ability to tailor rAAV for specific applications in gene therapy.…”