ADENOSINE DEAMINASE GENE REPLACEMENT THERAPY

  • Kellems, Rodney E, (PI)

Project: Research projectResearch Project

Description

Adenosine deaminase (ADA) is an enzyme of purine nucleoside metabolism that
is present in virtually all human tissues. The highest levels are found in
the thymus and are subject to developmental regulation within this tissue.
Individuals lacking ADA suffer from a genetic disorder termed severe
combined immunodeficiency disease characterized by a lack of B- and
T-lymphocytes. Thus, the genetic evidence indicates that ADA is essential
for development of the immune system. To address a number of questions
regarding ADA gene structure, the regulation of ADA gene expression, and
the molecular basis of ADA deficiency, we propose to clone the ADA gene
from cell lines we have isolated which have a 6,000-fold amplification of
the ADA gene. From these cloned sequences we propose to place ADA
minigenes in eukaryotic expression vectors for use in DNA mediated gene
transfer into ADA deficient cells. These studies will serve as a rational
beginning for the use of cloned ADA genes in gene replacement therapy. For
a number of reasons human ADA deficiency is an ideal model genetic disorder
for which to consider gene replacement therapy. The proposed research will
use recombinant DNA technology to analyze a specific human genetic
disorder. The information gained will be relevant not only for this one
genetic disease but to all human genetic disorders that become manifest in
bone marrow derived cells.
StatusFinished
Effective start/end date7/1/836/30/86

Funding

  • National Institutes of Health

Fingerprint

Adenosine Deaminase
Genetic Therapy
Inborn Genetic Diseases
Genes
Purine Nucleosides
Recombinant DNA
Genetic Models
Medical Genetics
Thymus Gland
Immune System
Clone Cells
Bone Marrow
Lymphocytes
Technology
Gene Expression
Cell Line
DNA

Keywords

  • Medicine(all)
  • Immunology and Microbiology(all)