Project: Research project

Project Details


Advances in molecular genetics have made it possible to consider
treating certain genetic diseases by somatic cell gene therapy,
i.e. by transferring copies of a normal gene into the somatic cells
of a patient in order to restore the function of the gene that is
involved. The field of gene therapy is in its infancy, therefore, it
is advantageous to investigate the efficacy of gene therapy in
animal models of human genetic disease. A group of animal
models that can be used for this purpose are cats and dogs with
mucopolysaccharidoses (MPS diseases), which are deficiencies in
the activities of lysosomal enzymes. The proposed experiments
will focus on the cat model of MPS VI, Maroteaux-Lamy
Syndrome, which is a deficiency in arylsulfatase-B (ASB) activity. Two of the prerequisites for efficatious gene therapy are that the
gene must be efficiently transferred to a sufficient number of
target cells in the patient and that the transferred gene must be
efficiently expressed in the target cells in vivo. In the proposed
experiments, the ASB gene will be inserted into retroviral vectors
(e.g. N2) which are very efficient in transferring genes into target
cells. Several vectors, containing various transcriptional
promotors, will be constructed in order to evaluate their relative
efficiency of expression and virus production. The ASB gene will
be transferred to MPS VI cells in vitro by infection with the
recombinant viruses and the target cells will be assayed for
enzyme activity and RNA expression from the transferred gene. The proposed experiments are necessary before expression of the
gene in vivo can be evaluated through actual attempts at gene
therapy in the MPS VI cats. Additionally, constructing retroviral
vectors that contain the ASB gene will make it possible to
directly investigate the molecular mechanisms of pathogenesis
within MPS VI cells by introducing a functional gene into a
diseased cell. Furthermore, the proposed experiments will enable
the investigators to transfer the recombinant DNA technology to
studies on gene therapy and molecular mechanisms of
pathogenesis in several other animal models of genetic diseases.
Effective start/end date9/15/872/29/88


  • National Institutes of Health


  • Medicine(all)


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