Journal Article

Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV

Nichol, Geoff, Surosky, Richard T, Tang, Winson W, Ando, Dale G, Tebas, Pablo, Collman, Ronald G, Gregory, Philip D, Stein, David, Spratt, S. Kaye, Kalos, Michael, Levine, Bruce L, Giedlin, Martin A, Frank, Ian, Wang, Shelley Q, Lee, Gary, Binder-Scholl, Gwendolyn, Holmes, Michael C, Hwang, Wei-Ting, June, Carl H, Plesa, Gabriela

2014

Overview

In this small study, investigators genetically disrupted the HIV receptor CCR5 in CD4 T cells of aviremic persons who were infected with HIV. After reinfusion and during viremia, the modified cells declined at a significantly slower rate than did the unmodified cells. The ability to make site-specific modifications to (or “edit”) the human genome has been an objective in medicine since the recognition of the gene as the basic unit of heredity. 1 , 2 The challenge of genome editing is the ability to generate a single double-strand break at a specific point in the DNA molecule. Numerous agents, including meganucleases, oligonucleotides that form DNA triplexes, and peptide nucleic acids, have been tested and shown to be limited by inefficiency. 3 – 5 Another class of reagents, the zinc-finger nucleases (ZFNs), have proved versatile for genome editing, and the use of ZFNs is now well established . . .

• Publisher: Massachusetts Medical Society
• Subject: Adult / Allergies / Antiretroviral Therapy, Highly Active / Biological and medical sciences / Blood Transfusion, Autologous / CCR5 protein / CD4 antigen / CD4-Positive T-Lymphocytes - chemistry / CD4-Positive T-Lymphocytes - transplantation / Chronic infection / Combined Modality Therapy / Deoxyribonucleic acid / DNA / DNA repair / DNA, Viral - blood / Female / General aspects / Genetic Therapy - adverse effects / Genetic Therapy - methods / Genome editing / Genomes / Highly active antiretroviral therapy / HIV / HIV - genetics / HIV - isolation & purification / HIV Infections - drug therapy / HIV Infections - immunology / HIV Infections - therapy / Human immunodeficiency virus / Human viral diseases / Humans / Immune reconstitution / Immunodeficiencies / Immunodeficiencies. Immunoglobulinopathies / Immunopathology / Infectious diseases / Leukocytes (mononuclear) / Lymphocyte Count / Lymphocyte Transfusion / Lymphocytes / Lymphocytes T / Male / Medical sciences / Middle Aged / Nuclease / Patients / Peripheral blood / Receptors, CCR5 - genetics / Rectum - immunology / Ribonucleic acid / RNA / RNA, Viral - blood / Viral diseases / Viral diseases of the lymphoid tissue and the blood. Aids / Viral Load / Viremia / Zinc finger proteins