Gene replacement therapy for inborn errors of purine metabolism.

Abstract

Effective retroviral vectors carrying the human HPRT and ADA genes have been described. Initial characterization of the retroviral gene transfer system using the HPRT vector allowed the delineation of several parameters important in viral titer, expression, and stability. Using the HPRT and ADA vectors, we have initiated experiments designed to insert these human genes into various tissues of the mouse and have demonstrated expression of both transduced genes in mouse bone marrow cells. Further work with these and other vector constructions is underway in the hope that this technique may allow safe and effective treatment of ADA and HPRT deficiencies, paving the way for treatments of other inborn errors of metabolism through somatic gene replacement therapy.

• Authors: D L Nelson, S M Chang, J Henkel-Tigges, K Wager-Smith, J W Belmont, C T Caskey
• Journal: Cold Spring Harbor symposia on quantitative biology (Cold Spring Harb Symp Quant Biol) Vol. 51 Pt 2 Pg. 1065-71 ( 1986) ISSN: 0091-7451 [Print] United States
• PMID: 3555977 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Hypoxanthine Phosphoribosyltransferase
• Adenosine Deaminase

Topics

• Adenosine Deaminase (deficiency, genetics)
• Animals
• Bone Marrow Cells
• Bone Marrow Transplantation
• Cell Line
• Cells, Cultured
• Genes
• Genetic Engineering (methods)
• Genetic Vectors
• Humans
• Hypoxanthine Phosphoribosyltransferase (deficiency, genetics)
• Mice
• Mice, Inbred Strains
• Purine-Pyrimidine Metabolism, Inborn Errors (genetics, therapy)
• Retroviridae (genetics)
• Transfection