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laboratory follows three main themes: |
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- studies on the
mechanisms of nuclear transport of plasmids
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- development of
nuclear targeting plasmid vectors for gene therapy of
the lung, eye and vasculature.
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- Effects of cyclic stretch on gene transfer
and expression in cultured cells and tissues
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Despite all of the hype regarding gene therapy, at
present, gene therapy is a dream due to insufficient levels of
gene transfer
and expression at desired sites. One way to increase gene expression
is to target more DNA to the cell nucleus. Since the nucleus is
the site of transcription, without the translocation of plasmid
DNA into the nucleus, no gene expression, or "gene therapy" can
take place. Ongoing projects in my laboratory are studying the
mechanisms of plasmid nuclear entry and exploiting what we learn
to improve gene therapy.
We have shown that plasmids are able to enter the nucleus in a
sequence-specific manner that appears to be mediated by transcription
factor binding. My lab is interested in identifying the proteins
required for this activity and the regulation of their nuclear
import. Based on our model, we have created cell-specific plasmids
by incorporating DNA sequences that bind to cell-specific transcription
factors. At present, we have examples of smooth muscle and endothelial
cell-targeting vectors that we hope to use for the treatment of
vascular proliferative diseases, and we are working to expand our
repertoire to selectively target expression to any desired cell
or tissue.
We also are developing methods for extracellular delivery of non-viral
vectors in animal models for disease. Using electroporation, we
have obtained very high levels of gene expression in the vasculature,
lungs, and eyes of animals. Our next goal is to combine our studies
on cell-specific plasmid nuclear import with this delivery method
to restrict expression to individual cell types and begin to focus
on attacking disease states.
For more detailed information on our research, follow the links
below: |
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