Abstract
The tremendous promise of gene therapy is stymied by inefficient gene transfer. Non-viral methods of transferring genes directly into tissues in situ have great potential for solving this problem. One attractive approach for non-viral direct gene transfer is the use of naked DNA. Previously, it was thought that naked DNA was able to express in only muscle and at low efficiency. We have recently found that naked DNA delivered intraportally can express at high levels in hepatocytes. Other non-viral methods of gene transfer are under development and these include ternary complexes of histone protein and liposomes. Besides trial-and-error approaches, the mechanism of the nuclear entry of plasmid DNA, a critical step, has been under intense study. It is anticipated that further advances in the efficiency of direct, non-viral gene transfer will enable its use in clinical settings in the near future.
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