GENETIC MODIFICATION OF PRIMATE HEMOPOIETIC REPOPULATING STEM CELLS

摘要

Genetic modification of pluripotent hemopoietic stem cells of primates (P-PHSC) by transduction of P-PHSC with a recombinantadeno-associated virus (AAV). The genome of the recombinant AAV comprises aDNA sequence flanked by the inverted terminal repeats(ITR) of AAV. The DNA sequence will normally comprise regulatory sequenceswhich are functional in hemopoietic cells and, controlledby these regulatory sequences, a sequence coding for a protein or RNA with atherapeutic property when introduced into hemopoietic cells.Preferred examples of DNA sequences are the human lysosomal glococerebrosidasegene, a globin gene from the human .beta.-globin genecluster, a DNA sequence encoding an RNA or protein with anti-viral activity,the .alpha. 1-antitrypsin gene and the human multidrug resistancegene I (MDRI). The invention provides for effective gene therapy with PHSC ofprimates, in particular humans.