Altering AAV tropism with mosaic viral capsids

L Gigout, P Rebollo, N Clement, K H Warrington, N Muzyczka, R M Linden, T Weber

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)

Abstract

Over the past decade, AAV-based vectors have emerged as promising candidates for gene therapeutic applications. Despite the broad tropism of the first eight serotypes identified, certain cell types are refractory to transduction with AAV-based vectors. Furthermore, for certain applications the targeting of specific cell types is desirable. To improve on present methods to alter AAV2 tropism, we take advantage of AAV2 mosaics. Here, we show that AAV2 mosaics have improved infectivity compared with all-mutant virions. Using an AAV2 mutant that contains the immunoglobulin-binding Z34C fragment of protein A, we demonstrate the utility of AAV2 mosaics to alter AAV2 tropism. This system allows us to transduce selectively and efficiently MO7e and Jurkat cells. The use of AAV2 mosaics with a protein A fragment inserted into their capsid, together with targeting antibodies, is a versatile method that allows the specific transduction of a wide array of cell types
Original languageEnglish
Pages (from-to)856 - 865
Number of pages10
JournalMolecular Therapy
Volume11
Issue number6
DOIs
Publication statusPublished - Jun 2005

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