Phase 2 gene therapy trial of an anti-HIV ribozyme in autologous CD34+ cells

被引：199

作者：

Mitsuyasu, Ronald T. ^{[1
]}

Merigan, Thomas C. ^{[2
]}

Carr, Andrew ^{[3
]}

Zack, Jerome A. ^{[4
]}

Winters, Mark A. ^{[2
]}

Workman, Cassy ^{[5
]}

Bloch, Mark ^{[6
]}

Lalezari, Jacob ^{[7
]}

Becker, Stephen ^{[8
]}

Thornton, Lorna ^{[8
]}

Akil, Bisher ^{[9
]}

Khanlou, Homayoon ^{[10
]}

Finlayson, Robert ^{[11
]}

McFarlane, Robert ^{[12
]}

Smith, Don E. ^{[13
]}

Garsia, Roger ^{[14
]}

Ma, David ^{[3
]}

Law, Matthew ^{[15
]}

Murray, John M. ^{[15
,16
]}

von Kalle, Christof ^{[17
,18
]}

Ely, Julie A. ^{[19
]}

Patino, Sharon M. ^{[19
]}

Knop, Alison E. ^{[19
]}

Wong, Philip ^{[19
]}

Todd, Alison V. ^{[19
]}

Haughton, Margaret ^{[19
]}

Fuery, Caroline ^{[19
]}

Macpherson, Janet L. ^{[19
]}

Symonds, Geoff P. ^{[19
]}

Evans, Louise A. ^{[19
]}

Pond, Susan M. ^{[19
]}

Cooper, David A. ^{[3
,15
]}

机构：

[1] Univ Calif Los Angeles, Ctr Clin AIDS Res & Educ, Los Angeles, CA 90035 USA

[2] Stanford Univ, Div Infect Dis & Geog Med, Stanford, CA 94305 USA

[3] St Vincents Clin, Darlinghurst, NSW 2010, Australia

[4] Univ Calif Los Angeles, Dept Med & Microbiol, Los Angeles, CA 90095 USA

[5] AIDS Res Initiat, Darlinghurst, NSW 2010, Australia

[6] Holdsworth House Med Practice, Darlinghurst, NSW 2010, Australia

[7] Quest Clin Res, San Francisco, CA 94115 USA

[8] Pacific Horizon Med Grp, San Francisco, CA 94115 USA

[9] Hlth Innovat Res, Los Angeles, CA 90069 USA

[10] AIDS Healthcare Fdn Res Ctr, Los Angeles, CA 90028 USA

[11] Taylor Sq Private Clin, Darlinghurst, NSW 2010, Australia

[12] E Sydney Doctors, Darlinghurst, NSW 2010, Australia

[13] Alb St Ctr, Darlinghurst, NSW 2010, Australia

[14] Royal Prince Alfred Hosp, Camperdown, NSW 2050, Australia

[15] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Darlinghurst, NSW 2010, Australia

[16] Univ New S Wales, Sch Math & Stat, Randwick, NSW 2052, Australia

[17] Cincinnati Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA

[18] German Canc Res Ctr, Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany

[19] Johnson & Johnson Res Proprietary Ltd, Sydney, NSW 1430, Australia

来源：

NATURE MEDICINE | 2009年 / 15卷 / 03期

基金：

美国国家卫生研究院;

关键词：

HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC GRANULOMATOUS-DISEASE; PERIPHERAL-BLOOD LYMPHOCYTES; T-LYMPHOCYTES; LENTIVIRAL VECTOR; TYPE-1; INFECTION; BONE-MARROW; TAR DECOY; REPLICATION; INHIBITION;

D O I：

10.1038/nm.1932

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Gene transfer has potential as a once-only treatment that reduces viral load, preserves the immune system and avoids lifetime highly active antiretroviral therapy. This study, which is to our knowledge the first randomized, double-blind, placebo-controlled, phase 2 cell-delivered gene transfer clinical trial, was conducted in 74 HIV-1-infected adults who received a tat-vpr-specific anti-HIV ribozyme (OZ1) or placebo delivered in autologous CD34(+) hematopoietic progenitor cells. There were no OZ1-related adverse events. There was no statistically significant difference in viral load between the OZ1 and placebo group at the primary end point (average at weeks 47 and 48), but time-weighted areas under the curve from weeks 40-48 and 40-100 were significantly lower in the OZ1 group. Throughout the 100 weeks, CD4(+) lymphocyte counts were higher in the OZ1 group. This study indicates that cell-delivered gene transfer is safe and biologically active in individuals with HIV and can be developed as a conventional therapeutic product.

引用

页码：285 / 292

页数：8

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