Journal article
Preclinical safety and efficacy of an anti-HIV-1 lentiviral vector containing a short hairpin RNA to CCR5 and the C46 fusion inhibitor
O Wolstein, M Boyd, M Millington, H Impey, J Boyer, A Howe, F Delebecque, K Cornetta, M Rothe, C Baum, T Nicolson, R Koldej, J Zhang, N Keech, J Camba Colón, L Breton, J Bartlett, DS An, IS Chen, B Burke Show all
Molecular Therapy Methods and Clinical Development | Published : 2014
DOI: 10.1038/mtm.2013.11
Open access
Abstract
Gene transfer has therapeutic potential for treating HIV-1 infection by generating cells that are resistant to the virus. We have engineered a novel self-inactivating lentiviral vector, LVsh5/C46, using two viral-entry inhibitors to block early steps of HIV-1 cycle. The LVsh5/C46 vector encodes a short hairpin RNA (shRNA) for downregulation of CCR5, in combination with the HIV-1 fusion inhibitor, C46. We demonstrate here the effective delivery of LVsh5/C46 to human T cell lines, peripheral blood mononuclear cells, primary CD4 + T lymphocytes, and CD34 + hematopoietic stem/progenitor cells (HSPC). CCR5-targeted shRNA (sh5) and C46 peptide were stably expressed in the target cells and were abl..
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Awarded by National Institutes of Health
Funding Acknowledgements
Funding for this work was provided in large part by Calimmune. O.W., M.B., M.M., H.I., F.D., J.Z., N.K., J.C.C., L.B., J.B., B.B., and G.P.S. are all employed by Calimmune. A.H., T.N., and R.K. were employed by Calimmune. Funding for Figure 7a,b were provided by NIH grants (NHLBI 1R01HL086409, 3R01HL086409-03S1, and NIAID 1R01AI100652-01A1 (D.S.A.)and AI55281 (I.S.Y.C.)).