Expression ofhumanadenosine deaminase inmicereconstituted withretrovirus-trans

Recombinant retroviruses encoding human adenosine deaminase (ADA;adenosine aminohydrolase, EC 3.5.4.4) havebeenusedtoinfect murine hematopoietic stem cells. Inbonemarrowtransplant recipients reconstituted with thegenetically modified cells, humanADA wasdetected in peripheral blood mononuclear cells oftherecipients foratleast 6months after transplantation. Inanimals analyzed indetail 4 months after transplantation, humanADAandproviral se- quences weredetected inallhematopoietic lineages; inseveral cases, humanADAactivity exceeded theendogenous activity. Thesestudies demonstrate thefeasibility ofintroducing a functional humanADAgeneinto hematopoietic stemcells and obtaining expression inmultiple hematopoietic lineages long after transplantation. Thisapproach should behelpful in designing effective genetherapies forsevere combined immu- nodeficiency syndromes inhumans. While somatic cell genetherapy isnowbeing considered in thetreatment ofavariety ofinherited andacquired diseases, genetic disorders thatselectively affect thehematopoietic system havebeenthefocus ofmostresearch, because the appropriate target cell forgenetransfer, thehematopoietic stemcell, iseasily accessed, manipulated invivo, andtrans- planted. Foravariety ofreasons, aninherited deficiency of theenzymeadenosine deaminase (ADA;adenosine amino- hydrolase, EC3.5.4.4) hasbeenconsidered anideal candi-