HIV

Lead Indication Approach Program Research Preclinical Phase 1/2 Phase 3
ZFN (knockout) SB-728-T
Research Phase complete
Preclinical Phase complete
Phase 1/2 Phase in progress
Phase 3 Phase not started

Sangamo Therapeutics' approach uses ZFN-mediated genome editing in T-cells to replicate a naturally occurring human mutation which renders individuals largely resistant to infection with the most common strain of HIV. Sangamo has an open label Phase 2 clinical study to evaluate safety and efficacy of SB-728-T in T-cells.

ZFN (knockout) SB-728-HSPC
Research Phase complete
Preclinical Phase complete
Phase 1/2 Phase in progress
Phase 3 Phase not started

Sangamo Therapeutics’ approach uses ZFN-mediated genome editing in HSCs to replicate a naturally occurring human mutation which renders individuals largely resistant to infection with the most common strain of HIV. An investigator sponsored open label Phase 1/2 clinical study to evaluate safety and efficacy of SB-728-HSPC in stem cells.

About HIV/AIDS

HIV infection results in the death of immune system cells, particularly CD4+ T-cells leading to AIDS, a condition in which the body's immune system is depleted to such a degree that the patient is unable to fight off common infections.

There are now more than 36.9 million people living with HIV and AIDS worldwide

All disease statistics are according to the Centers of Disease Control and Prevention (CDC)

>2 Million

People newly infected with HIV

CDC, 2014

~1.2 Million

People died of AIDS-related illnesses

CDC, 2014

~1.2 Million

People living with HIV/AIDS in the United States

CDC, 2012 (the most recent data available)

~12.8%

Were unaware that they were infected

CDC, 2012 (the most recent data available)

Our Therapeutic Approach

SB-728-T

Our therapeutic approach aims to use our ZFN-mediated genome editing technology to replicate a naturally occurring human mutation, which renders individuals largely resistant to infection with the most common strain of HIV. CCR5 is a co-receptor for HIV entry into T-cells and if CCR5 is not expressed on their surface HIV infects them with lower efficiency.

The CCR5 delta-32 mutation affords protection from HIV infection

A population of individuals that is immune to HIV infection, despite multiple exposures to the virus, has been identified and extensively studied. The majority of these individuals have a natural mutation, CCR5 delta-32, of both of their CCR5 gene copies (homozygous), resulting in the expression of a shortened, non-functional CCR5 protein. This mutation appears to have no observable deleterious effect. Individuals who carry the CCR5 delta-32 mutation in only one of their two CCR5 gene copies (heterozygotes), tend to take longer to develop AIDS and are classified as so-called "long-term non-progressors."

In addition, a study published in Blood in December 2010 reported an effective cure when an AIDS patient with leukemia received a bone marrow transplant from a "matched" donor who was homozygous for this delta-32 CCR5 mutation. This approach transferred the hematopoietic stem cells (HSCs) residing from the bone marrow of the delta-32 donor, and provided a self-renewable and potentially lifelong source of HIV-resistant immune cells. After transplantation, the AIDS patient was able to discontinue all anti-HIV drug treatments (ART), CD4 counts increased and viral load dropped to an undetectable level, demonstrating effective transplantation of protection from HIV infection. The subject remains off ART and is widely considered to be cured of his HIV infection.

Using CCR5 mutations for therapeutic advantage

We are using our ZFN-mediated genome editing technology to knock out the CCR5 gene in cells of a patient’s immune system (both T-cells and hematopoietic stem cells (HSCs) which give rise to T-cells) to make these cells permanently resistant to HIV infection. The aim is to provide a population of HIV-resistant cells that can fight HIV and opportunistic infections thereby mimicking the characteristics of individuals that carry the natural CCR5 delta-32 mutation.

Clinical Trials

Clinical Trials

Please visit the Clinicaltrials.gov webpage to learn more about our clinical trials in HIV/AIDS.

Presentations + Publications

Preclinical development and qualification of ZFN-mediated CCR5 disruption in human hematopoietic stem/progenitor cells.

DiGiusto DL, Cannon PM, Holmes MC, Li L, Rao A, Wang J, Lee G, Gregory PD, Kim KA, Hayward SB, Meyer K, Exline C, Lopez E, Henley J, Gonzalez N, Bedell V, Stan R, Zaia JA.
Mol Ther Methods Clin Dev. 2016 Nov 9;3:16067

Genomic editing of the HIV-1 coreceptor CCR5 in adult hematopoietic stem and progenitor cells using zinc finger nucleases.

Li L, Krymskaya L, Wang J, Henley J, Rao A, Cao LF, Tran CA, Torres-Coronado M, Gardner A, Gonzalez N, Kim K, Liu PQ, Hofer U, Lopez E, Gregory PD, Liu Q, Holmes MC, Cannon PM, Zaia JA, DiGiusto DL.
Mol Ther. 2013 Jun;21(6):1259-69. doi: 10.1038/mt.2013.65

Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo.

Holt N, Wang J, Kim K, Friedman G, Wang X, Taupin V, Crooks GM, Kohn DB, Gregory PD, Holmes MC, Cannon PM.
Nat Biotechnol. 2010 Aug;28(8):839-47. doi: 10.1038/nbt.1663

Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV.

Tebas P, Stein D, Tang WW, Frank I, Wang SQ, Lee G, Spratt SK, Surosky RT, Giedlin MA, Nichol G, Holmes MC, Gregory PD, Ando DG, Kalos M, Collman RG, Binder-Scholl G, Plesa G, Hwang WT, Levine BL, June CH.
N Engl J Med. 2014 Mar 6;370(10):901-10. doi: 10.1056/NEJMoa1300662.


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