TY - JOUR
T1 - Altering AAV tropism with mosaic viral capsids
AU - Gigout, Laure
AU - Rebollo, Patricia
AU - Clement, Nathalie
AU - Warrington, Kenneth H.
AU - Muzyczka, Nicholas
AU - Linden, R. Michael
AU - Weber, Thomas
N1 - Funding Information:
This article is dedicated to Josef Brunner (Swiss Federal Institute of Technology, Zqrich, Switzerland), on the occasion of his retirement, for introducing me (T.W.) to science. We thank Jqrgen Kleinschmidt (Deutsches Krebsforschungszentrum, Heidelberg, Germany) for providing us with the plasmid pDG and Jonathan Licht (Mount Sinai School of Medicine, New York, NY, USA) for giving us MO7e cells. This work was supported by NIH Grants GM062234 and DK062345 (R.M.L) and PO1 HL51811 and PO1 HL59412 and the Edward R. Koger Chair (N.M.). N.M. and K.H.W are investors on patents related to recombinant AAV technology and N.M owns equity in a gene therapy company that is commercializing AAV for gene therapy applications.
PY - 2005/6
Y1 - 2005/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=18444380824&partnerID=8YFLogxK
U2 - 10.1016/j.ymthe.2005.03.005
DO - 10.1016/j.ymthe.2005.03.005
M3 - Article
C2 - 15922956
AN - SCOPUS:18444380824
SN - 1525-0016
VL - 11
SP - 856
EP - 865
JO - Molecular Therapy
JF - Molecular Therapy
IS - 6
ER -