Gene therapy using ribozymes
Some RNA molecules, termed ribozymes, have been shown to have catalytic activity.
We are attempting use hairpin and hammerhead ribozymes as tools for gene therapy.
Ribozymes might be particularly useful in controlling dominant negative genetic
diseases--disorders associated with the expression of a single mutant allele.
We are designing ribozymes to block retinal degeneration in certain forms of retinitis
pigmentosa and have tested these in animal models of this dominant genetic disorder
using Adeno-Associated Virus (AAV) vectors. We are extending this approach to combat
diseases affecting the brain (Huntington Disease), peripheral nervous system (ALS)
and heart (familial hypertrophic cardiomyopathy).
Disease models
We also use the tools of gene therapy to learn more about disease. Virally vectored ribozymes or dominant mutant genes can also be used to create animal models of human disease or to ask specific questions concerning pathogenesis. We have used AAV-delivered ribozymes to create mouse models of mitochondrial diseases, which are unattainable using transgenic approaches because of embryonic lethality. We are working on a similar approach to obtain a faithful animal model of Parkinson Disease and of Age-Related Macular Degeneration.
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