Gene Transfer in Humans Using a Conditionally Replicating Lentiviral Vector

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 Nov 9

PMID 17090675

Citations 220

Authors

Bruce L Levine

Laurent M Humeau

Jean Boyer

Rob-Roy MacGregor

Tessio Rebello

Xiaobin Lu

Gwendolyn K Binder

Vladimir Slepushkin

Franck Lemiale

John R Mascola

Frederic D Bushman

Boro Dropulic

Carl H June

Affiliations

Soon will be listed here.

Abstract

We report findings from a clinical evaluation of lentiviral vectors in a phase I open-label nonrandomized clinical trial for HIV. This trial evaluated the safety of a conditionally replicating HIV-1-derived vector expressing an antisense gene against the HIV envelope. Five subjects with chronic HIV infection who had failed to respond to at least two antiviral regimens were enrolled. A single i.v. infusion of gene-modified autologous CD4 T cells was well tolerated in all patients. Viral loads were stable, and one subject exhibited a sustained decrease in viral load. CD4 counts remained steady or increased in four subjects, and sustained gene transfer was observed. Self-limiting mobilization of the vector was observed in four of five patients. There is no evidence for insertional mutagenesis after 21-36 months of observation. Immune function improved in four subjects. Lentiviral vectors appear promising for gene transfer to humans.

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