Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Sci Transl Med ; 11(503)2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31366580

RESUMO

Reactivation of fetal hemoglobin (HbF) is being pursued as a treatment strategy for hemoglobinopathies. Here, we evaluated the therapeutic potential of hematopoietic stem and progenitor cells (HSPCs) edited with the CRISPR-Cas9 nuclease platform to recapitulate naturally occurring mutations identified in individuals who express increased amounts of HbF, a condition known as hereditary persistence of HbF. CRISPR-Cas9 treatment and transplantation of HSPCs purified on the basis of surface expression of the CD34 receptor in a nonhuman primate (NHP) autologous transplantation model resulted in up to 30% engraftment of gene-edited cells for >1 year. Edited cells effectively and stably reactivated HbF, as evidenced by up to 18% HbF-expressing erythrocytes in peripheral blood. Similar results were obtained by editing highly enriched stem cells, defined by the markers CD34+CD90+CD45RA-, allowing for a 10-fold reduction in the number of transplanted target cells, thus considerably reducing the need for editing reagents. The frequency of engrafted, gene-edited cells persisting in vivo using this approach may be sufficient to ameliorate the phenotype for a number of genetic diseases.


Assuntos
Sistemas CRISPR-Cas/genética , Hemoglobina Fetal/metabolismo , Células-Tronco Hematopoéticas/citologia , Animais , Antígenos CD34/metabolismo , Hemoglobina Fetal/genética , Edição de Genes , Genótipo , Transplante de Células-Tronco Hematopoéticas , Humanos , Macaca mulatta , Primatas , Antígenos Thy-1/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...