Retroviral gene transfer and sustained expression of human arylsulfatase A.
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| Abstract |
Transduction of mouse hematopoietic stem cells and their progeny was studied using a recombinant retroviral vector (MFG-ASA) which incorporates the human arylsulfatase A gene (ASA; EC 3.1.6.8). Successful transduction was demonstrated in spleen colonies of mice that received bone marrow transplantation, cultured bone marrow-derived macrophages, visceral tissues and brain of long-term reconstituted mice, and also the spleen colonies of secondarily transplanted mice. The efficiency of transduction in primary spleen colonies was 90%. Expression of the ASA transgene exceeded endogenous levels in spleen colonies and in cultured macrophages by 50-100%. Enzyme activity in the visceral tissues of long-term reconstituted mice consistently showed elevated ASA activity, greater than three-fold in the spleen and lung of one animal. Increased activity of ASA also could be detected in secondary spleen colonies. These data demonstrate the usefulness of the MFG-ASA vector for efficient gene transfer and expression in mouse hematopoietic stem cells and their differentiated progeny. The presence of vector DNA in the brain 4 months after transplantation suggests a role for gene transfer and stem cell transplantation in the treatment strategies for metachromatic leukodystrophy.
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| Authors | R Learish, T Ohashi, P A Robbins, A Bahnson, S S Boggs, K Patrene, B E Schwartz, V Gieselmann, J A Barranger |
| Journal | Gene therapy (Gene Ther) Vol. 3 Issue 4 Pg. 343-9 (Apr 1996) ISSN: 0969-7128 [Print] England |
| PMID | 8732166 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
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