Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.4.4 (adenosine deaminase)
 5,136 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reports of 1- to 2-log higher gene transfer levels in purified CD34+ cells or marrow CFU compared with levels in mature circulating blood cells after transplantation of retrovirally transduced primitive human hematopoietic cells have resulted in concern that transduced progenitors do not contribute proportionally to ongoing hematopoiesis (Kohn et al., 1995; Brenner, 1996). To study the issue in a relevant large animal, we analyzed samples of mature blood cells, marrow CD34-enriched cells and marrow CD34-depleted cells, and marrow CFU from a cohort of 11 rhesus transplanted with retrovirally transduced cells and followed for up to 5.5 years. They were transplanted with CD34-enriched bone marrow (BM) or G-CSF/SCF-mobilized peripheral blood (PB) cells transduced with vectors containing either neo, human glucocerebrosidase, or murine adenosine deaminase genes. There were no significant differences between the levels of vector sequences found in BM CD34+ cells, BM CD34- cells, PB granulocytes, or PB mononuclear cells (MNCs) in any animal. In four animals transplanted with SCF/G-CSF-primed BM cells and analyzed 3-6 months posttransplantation, the percentage of CFU containing the neo vector appeared to be 1 log higher than the representation of marked cells in the PB of these animals, but this discrepancy did not persist at time points greater than 6 months posttransplantation. The level of CFU marking was no higher than PB granulocyte or MNC marking at any time points in the other animals. Low levels of mature gene-modified cells probably reflect poor transduction of repopulating stem cells, not a block in differentiation or specific immune rejection of mature cells. This study represents the longest follow-up of primates transplanted with transduced hematopoietic cells, and it is encouraging that the levels of vector-containing cells appear stable for up to 5 years.
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PMID:No discrepancy between in vivo gene marking efficiency assessed in peripheral blood populations compared with bone marrow progenitors or CD34+ cells. 1009 6

The era of molecular biology has led to the development of powerful tools capable of generating therapeutics for genetic disorders. Although there is much current emphasis placed on the development of 'gene therapy' for human disease, developments in the production and availability of recombinant proteins are likely to have a more substantial impact on genetic disease in the short term. The clinical evaluation of recombinant or purified proteins serves as an initial 'proof of principle' of gene-based therapies and thus should expedite advances in this area. Current examples include the use of bovine adenosine deaminase for a form of severe combined immune deficiency (SCID) (Hilman BC, Sorensen RU. Management options: SCIDS with adenosine deaminase deficiency. Ann Allergy 72: 1994: 395-403) and glucocerebrosidase for Gaucher disease (Niederau C, vom Dahl S, Haussinger D. First long-term results of imiglucerase therapy of type 1 Gaucher disease. Eur J Med Res 1998: 3: 25-30). The success of these two enzyme replacement regimes in human clinical trials has been a main impetus for the development of gene-based therapies for these disorders. The 'molecularization of medicine' has led to a more thorough understanding of the molecular basis of disease and disease pathogenesis. The availability of recombinant proteins and the development of appropriate delivery systems will result in more widespread use of these agents. Protein engineering will generate agents with novel functions as is already witnessed with the generation of fusion proteins. This review will highlight advances in the use of recombinant proteins for genetic disease and future potential uses of recombinant proteins.
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PMID:Recombinant proteins for genetic disease. 1045 Aug 55