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

Nature Medicine

Volumn 15, Issue 3, 2009, Pages 285-292

  Mitsuyasu, Ronald T ^a   Merigan, Thomas C ^b   Carr, Andrew ^c   Zack, Jerome A ^d   Winters, Mark A ^b   Workman, Cassy ^e   Bloch, Mark ^f   Lalezari, Jacob ^g   Becker, Stephen ^h   Thornton, Lorna ^h   Akil, Bisher ⁱ   Khanlou, Homayoon ^j   Finlayson, Robert ^k   McFarlane, Robert ^l   Smith, Don E ^k   Garsia, Roger ^m   Ma, David ^c   Law, Matthew ⁿ   Murray, John M ^n,o   Von Kalle, Christof ^p,q   Ely, Julie A ^r   Patino, Sharon M ^r   Knop, Alison E ^r   Wong, Philip ^r   Todd, Alison V ^r   Haughton, Margaret ^r   Fuery, Caroline ^r   Macpherson, Janet L ^r   Symonds, Geoff P ^r   Evans, Louise A ^r   Pond, Susan M ^r   Cooper, David A ^c,n   more..

^a UNIVERSITY OF CALIFORNIA   (United States)

^b STANFORD UNIVERSITY   (United States)

^c ST VINCENT S HOSPITAL   (Australia)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e AIDS Research Initiative   (Australia)

^f Holdsworth House General Practice   (Australia)

^g Quest Clinical Research   (United States)

^h Pacific Horizon Medical Group   (United States)

ⁱ Health Innovations Research   (United States)

^j AIDS HEALTHCARE FOUNDATION   (United States)

^k East Sydney Doctors ^*  (Australia)

^l East Sydney Doctors   (Australia)

^m ROYAL PRINCE ALFRED HOSPITAL   (Australia)

ⁿ UNIVERSITY OF NEW SOUTH WALES   (Australia)

^o UNIVERSITY OF NEW SOUTH WALES   (Australia)

^p CINCINNATI CHILDREN S HOSPITAL RESEARCH FOUNDATION   (United States)

^q GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^r JOHNSON AND JOHNSON   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ANTIRETROVIRUS AGENT; CD34 ANTIGEN; CD4 ANTIGEN; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; OZ 1; PLACEBO; UNCLASSIFIED DRUG;

ADULT; ALANINE AMINOTRANSFERASE BLOOD LEVEL; AREA UNDER THE CURVE; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION; CARDIOTOXICITY; CD4 LYMPHOCYTE COUNT; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; FEMALE; GENE THERAPY; GENE TRANSFER; HEADACHE; HEPATOMEGALY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE SYSTEM; LIFESPAN; LYMPHOCYTE COUNT; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; MUSCULOSKELETAL PAIN; NEPHROTOXICITY; NEUTROPENIA; NONHUMAN; PHASE 2 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RIBOZYME THERAPY; RIBOZYME VECTOR; SIDE EFFECT; THROMBOCYTE COUNT; THROMBOCYTOPENIA; VIRAL GENE DELIVERY SYSTEM; VIROTHERAPY; VIRUS LOAD;

ADULT; ANTIGENS, CD34; BASE SEQUENCE; DOUBLE-BLIND METHOD; FEMALE; GENE THERAPY; HIV INFECTIONS; HIV-1; HUMANS; MALE; PLACEBOS; RNA, CATALYTIC; VIRAL LOAD;

HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 62049083710     PISSN: 10788956     EISSN: 1546170X     Source Type: Journal    
DOI: 10.1038/nm.1932     Document Type: Article

References (46)

1. Taylor, B.S., Sobieszczyk, M.E., McCutchan, F.E. & Hammer, S.M. The challenge of HIV-1 subtype diversity. N. Engl. J. Med. 358-1590-1602 (2008).
2. Watkins, D.I., Burton, D.R., Kallas, E.G., Moore, J.P. & Koff, W.C. Nonhuman primate models and the failure of the Merck HIV-1 vaccine in humans. Nat. Med. 14, 617-621 (2008).
3. Baltimore, D. Gene therapy. Intracellular immunization. Nature 335, 395-396 (1988).
4. Amado, R.G. et al. Anti-human immunodeficiency virus hematopoietic progenitor cell-delivered ribozyme in a phase I study: myeloid and lymphoid reconstitution in human immunodeficiency virus type-1-infected patients. Hum. Gene Ther. 15, 251-262 (2004).
5. An, D.S. et al. Stable reduction of CCR5 by RNAi through hematopoietic stem cell transplant in non-human primates.. Proc. Natl. Acad. Sci. USA 104, 13110-13115 (2007).
6. Anderson, J. et al. Safety and efficacy of a lentiviral vector containing three anti-HIV genes-CCR5 ribozyme, tat-rev siRNA, and TAR decoy-in SCID-hu mouse-derived T cells. Mol. Ther. 15, 1182-1188 (2007).
7. Bahner, I. et al. Comparison of trans-dominant inhibitory mutant human immunodeficiency virus type 1 genes expressed by retroviral vectors in human T lymphocytes. J. Virol. 67, 3199-3207 (1993).
8. Cagnon, L. & Rossi, J. Retroviral delivery and anti-HIV testing of hammerhead ribozymes. Methods Mol. Biol. 74, 451-457 (1997).
9. Dropulic, B., Elkins, D.A., Rossi, J.J. & Sarver, N. Ribozymes: use as anti-HIV therapeutic molecules. Antisense Res. Dev. 3, 87-94 (1993).
10. Fanning, G., Amado, R. & Symonds, G. Gene therapy for HIV/AIDS: the potential for a new therapeutic regimen. J. Gene Med. 5, 645-653 (2003).
11. Kohn, D.B. Gene therapy using hematopoietic stem cells. Curr. Opin. Mol. Ther. 1, 437-442 (1999).
12. + cells from the bone marrow of human immunodeficiency virus-1-infected children. Blood 94, 368-371 (1999).
13. Li, M., Li, H. & Rossi, J.J. RNAi in combination with a ribozyme and TAR decoy for treatment of HIV infection in hematopoietic cell gene therapy. Ann. NY Acad. Sci. 1082, 172-179 (2006).
14. Lo, A.S., Zhu, Q. & Marasco, W.A. Intracellular antibodies (intrabodies) and their therapeutic potential. Handb. Exp. Pharmacol. 181, 343-373 (2008).
15. Marasco, W.A., LaVecchio, J. & Winkler, A. Human anti-HIV-1 tat sFv intrabodies for gene therapy of advanced HIV-1-infection and AIDS. J. Immunol. Methods 231, 223-238 (1999).
16. Mautino, M.R. & Morgan, R.A. Potent inhibition of human immunodeficiency virus type 1 replication by conditionally replicating human immunodeficiency virus-based lentiviral vectors expressing envelope antisense mRNA. Hum. Gene Ther. 11, 2025-2037 (2000).
17. + T lymphocytes engineered with antihuman immunodeficiency virus (HIV) genes in HIV-infected individuals. Hum. Gene Ther. 16, 1065-1074 (2005).
18. Morris, K.V. & Rossi, J.J. Lentivirus-mediated RNA interference therapy for human immunodeficiency virus type 1 infection. Hum. Gene Ther. 17, 479-486 (2006).
19. Rossi, J.J. The application of ribozymes to HIV infection. Curr. Opin. Mol. Ther. 1, 316-322 (1999).
20. Strayer, D.S. et al. Current status of gene therapy strategies to treat HIV/AIDS. Mol. Ther. 11, 823-842 (2005).
21. Taylor, J.A. et al. Foamy virus vectors expressing anti-HIV transgenes efficiently block HIV-1 replication. Mol. Ther. 16, 46-51 (2008).
22. von Laer, D., Hasselmann, S. & Hasselmann, K. Gene therapy for HIV infection: what does it need to make it work? J. Gene Med. 8, 658-667 (2006).
23. Zahn, R.C. et al. Efficient entry inhibition of human and nonhuman primate immunodeficiency virus by cell surface-expressed gp41-derived peptides. Gene Ther. 15, 1210-1222 (2008).
24. Sarver, N. et al. Ribozymes as potential anti-HIV-1 therapeutic agents. Science 247, 1222-1225 (1990).
25. Schambach, A. et al. Towards hematopoietic stem cell-mediated protection against infection with human immunodeficiency virus. Gene Ther. 13, 1037-1047 (2006).
26. Rossi, J.J., June, C.H. & Kohn, D.B. Genetic therapies against HIV. Nat. Biotechnol. 25, 1444-1454 (2007).
27. Macpherson, J.L., Ely, J.A., Sun, L.Q. & Symonds, G.P. Ribozymes in gene therapy of HIV-1. Front. Biosci. 4, D497-D505 (1999).
28. Levine, B.L. et al. Gene transfer in humans using a conditionally replicating lentiviral vector. Proc. Natl. Acad. Sci. USA 103, 17372-17377 (2006).
29. + T lymphocytes in HIV-infected patients. J. Gene Med. 7, 552-564 (2005).
30. +) cells. Mol. Ther. 12, 77-86 (2005).
31. Sun, L.Q., Ely, J.A., Gerlach, W. & Symonds, G. Anti-HIV ribozymes. Mol. Biotechnol. 7, 241-251 (1997).
32. Sun, L.Q., Wang, L., Gerlach, W.L. & Symonds, G. Target sequence-specific inhibition of HIV-1 replication by ribozymes directed to tat RNA. Nucleic Acids Res. 23, 2909-2913 (1995).
33. Sun, L.Q. et al. Resistance to human immunodeficiency virus type 1 infection conferred by transduction of human peripheral blood lymphocytes with ribozyme, antisense, or polymeric trans-activation response element constructs. Proc. Natl. Acad. Sci. USA 92, 7272-7276 (1995).
34. Rossi, J.J. Ribozyme therapy for HIV infection. Adv. Drug Deliv. Rev. 44, 71-78 (2000).
35. Wang, L. et al. Preclinical characterization of an anti-tat ribozyme for therapeutic application. Hum. Gene Ther. 9, 1283-1291 (1998).
36. Center for Biologics Evaluation and Research. Guidance for Industry: Gene Therapy Clinical Trials - Observing Subjects for Delayed Adverse Events. (US Department of Health and Human Services, Rockville, Maryland, 2006).
37. Center for Biologics Evaluation and Research. Guidance for Industry: Supplemental Guidances on Testing for Replication Competent Retrovirus in Retroviral Vector Based Gene Therapy Products and During Follow-up of Patients in Clinical Trials Using Retroviral Vectors. (US Department of Health and Human Services, Rockville, Maryland, 2006).
38. Cavallaro, A.M. et al. Three to six year follow-up of normal donors who received recombinant human granulocyte colony-stimulating factor. Bone Marrow Transplant. 25, 85-89 (2000).
39. Nicolini, F.E. et al. Long-term persistent lymphopenia in hematopoietic stem cell donors after donation for donor lymphocyte infusion. Exp. Hematol. 32, 1033-1039 (2004).
40. Novotny, J. et al. Sustained decrease of peripheral lymphocytes after allogeneic blood stem cell aphereses. Br. J. Haematol. 100, 695-697 (1998).
41. Malech, H.L. et al. Prolonged production of NADPH oxidase-corrected granulocytes after gene therapy of chronic granulomatous disease. Proc. Natl. Acad. Sci. USA 94, 12133-12138 (1997).
42. Aiuti, A. et al. Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning. Science 296, 2410-2413 (2002).
43. Hacein-Bey-Abina, S. et al. LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1. Science 302, 415-419 (2003).
44. Ott, M.G. et al. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat. Med. 12, 401-409 (2006).
45. + count-guided interruption of antiretroviral treatment. N. Engl. J. Med. 355, 2283-2296 (2006).
46. Schmidt, M. et al. High-resolution insertion-site analysis by linear amplification-mediated PCR (LAM-PCR). Nat. Methods 4, 1051-1057 (2007).