Expression of human adenosine deaminase from various strong promoters after gene transfer into human hematopoietic cell lines.

Important note: Information in this article was accurate in 1989. The state of the art may have changed since the publication date.

Expression of human adenosine deaminase from various strong promoters after gene transfer into human hematopoietic cell lines.

Blood. 1989 Aug 1;74(2):876-81. Unique Identifier : AIDSLINE MED/89323444
Hock RA; Miller AD; Osborne WR; Program in Molecular Medicine, Fred Hutchinson Cancer Research; Center, Seattle, WA 98104.

Abstract: Adenosine deaminase (ADA) deficiency is associated with a fatal severe combined immunodeficiency. Because most patients do not have a suitable marrow donor, the introduction of a normal ADA gene into the patient's marrow cells is a potentially useful alternative therapy. To identify vectors that provide optimal gene expression in human hematopoietic cells, we investigated retroviral vectors containing the ADA gene under the transcriptional control of the promoter/enhancers of Moloney murine leukemia virus, the simian virus 40 early region, the cytomegalovirus immediate-early gene, the lymphotropic papovavirus, and the human beta-globin gene. ADA expression from these vectors was monitored in the ADA- human histiocytic lymphoma cell line DHL-9, and in the multipotential chronic myeloid leukemia cell line K562. ADA expression in infected K562 cells was also measured after induction of megakaryoblastic differentiation by phorbol ester, and after induction of erythroid differentiation by sodium n-butyrate or hemin. In these hematopoietic cell lines, the vectors that contained ADA controlled by either the Moloney murine leukemia virus promoter (LASN) or the cytomegalovirus promoter (LNCA) expressed ADA at much higher levels than the other vectors tested. Furthermore, in K562 cells infected with LASN and LNCA vectors, induction of terminal differentiation resulted in the same or higher level expression of ADA. These cell lines have permitted the evaluation of transduced gene expression in proliferating and differentiating hematopoietic cells that provide a model for bone marrow-targeted gene therapy.

Keywords: Adenosine Deaminase/*GENETICS Animal Cell Line Cloning, Molecular Genes, Structural Genetic Vectors Hematopoietic Stem Cells/*ENZYMOLOGY Human Leukemia, Erythroblastic, Acute/ENZYMOLOGY/GENETICS Lymphoma/ENZYMOLOGY/GENETICS Mice Nucleoside Deaminases/*GENETICS *Promoter Regions (Genetics) Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. *Transfection Tumor Cells, Cultured/ENZYMOLOGY JOURNAL ARTICLE

891130
M89B0536

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1989. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1989. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .