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First reported by Positively Aware
in January 2010, research on the use of zinc finger nuclease technology to
battle HIV has been one of the promising gene therapies in development. Pablo
Tebas, MD, presented additional data from the first zinc finger nuclease
(SB-728) cohorts at CROI and ICAAC last year and scientists at The Scripps
Research Institute have now shown that a new technique may be a safer
alternative to current experimental gene therapy against HIV infection.
“We showed that we can modify the
genomes of cells without the troubles that have long been linked to traditional
gene therapy techniques,” said the study's senior author Carlos F. Barbas , the
Janet and Keith Kellogg Professor of Molecular Biology and Chemistry at The Scripps
Research Institute.
The new technique, reported in
Nature Methods, employs zinc finger nuclease (ZFN) proteins, which can bind and
cut DNA at precisely defined locations in the genome. ZFNs are coming into
widespread use in scientific experiments and potential disease treatments, but
typically are delivered into cells using potentially risky gene therapy
methods.
The Scripps Research scientists
simply added ZFN proteins directly to cells in a lab dish and found that the
proteins crossed into the cells and performed their gene-cutting functions with
high efficiency and minimal collateral damage.
“This work removes a major
bottleneck in the efficient use of ZFN proteins as a gene therapy tool in
humans,” said Michael K. Reddy, who oversees transcription mechanism grants at
the National Institutes of Health's (NIH) National Institute of General Medical
Sciences, which helped fund the work, along with an NIH Director's Pioneer
Award. “The directness of Dr. Barbas's approach of 'simply' testing the notion
that ZFNs could possess an intrinsic cell-penetrating ability is a testament to
his highly creative nature and further validates his selection as a 2010
recipient of an NIH Director's Pioneer Award.”
Scientists had assumed that ZFN
proteins cannot cross cell membranes, so the standard ZFN delivery method has
been a gene-therapy technique employing a relatively harmless virus to carry a
designer ZFN gene into cells. Once inside, the ZFN gene starts producing ZFN
proteins, which seek and destroy their target gene within the cellular DNA.
One risk of the gene-therapy
approach is that viral DNA—even if the virus is not a retrovirus—may end up
being incorporated randomly into cellular DNA, disrupting a valuable gene such
as a tumor-suppressor gene. Another risk with this delivery method is that ZFN
genes will end up producing too many ZFN proteins, resulting in a high number
of “off-target” DNA cuts. The viral delivery approach involves a lot of
off-target damage, according to Barbas, and it is hoped that the new
methodology will enable scientists to avoid such damage.
The Friends of AIDS Foundation is
dedicated to enhancing the quality of life for HIV positive individuals and
empowering people to make healthy choices to prevent the spread of the HIV
virus. To learn more about The Friends of AIDS Foundation, please visit: http://www.friendsofaids.org.
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