CRISPR-Edited Stem Cells in a Patient with HIV and Acute Lymphocytic Leukemia.
N Engl J Med
; 381(13): 1240-1247, 2019 09 26.
Article
em En
| MEDLINE
| ID: mdl-31509667
ABSTRACT
The safety of CRISPR (clustered regularly interspaced short palindromic repeats)-based genome editing in the context of human gene therapy is largely unknown. CCR5 is a reasonable but not absolutely protective target for a cure of human immunodeficiency virus type 1 (HIV-1) infection, because CCR5-null blood cells are largely resistant to HIV-1 entry. We transplanted CRISPR-edited CCR5-ablated hematopoietic stem and progenitor cells (HSPCs) into a patient with HIV-1 infection and acute lymphoblastic leukemia. The acute lymphoblastic leukemia was in complete remission with full donor chimerism, and donor cells carrying the ablated CCR5 persisted for more than 19 months without gene editing-related adverse events. The percentage of CD4+ cells with CCR5 ablation increased by a small degree during a period of antiretroviral-therapy interruption. Although we achieved successful transplantation and long-term engraftment of CRISPR-edited HSPCs, the percentage of CCR5 disruption in lymphocytes was only approximately 5%, which indicates the need for further research into this approach. (Funded by the Beijing Municipal Science and Technology Commission and others; ClinicalTrials.gov number, NCT03164135.).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Hematopoéticas
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Infecções por HIV
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HIV-1
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Transplante de Células-Tronco Hematopoéticas
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Receptores CCR5
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Sistemas CRISPR-Cas
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Edição de Genes
Limite:
Adult
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article