gene-therapy method that doesn't rely on potentially
toxic viruses as vectors may be growing closer as
the result of in vitro research results reported by
UB scientists in the current online issue of the Proceedings
of the National Academy of Sciences.
paper, which describes the successful uptake of a
fluorescent gene by cells using novel nanoparticles
developed as DNA carriers at UB, demonstrates that
the nanoparticles ultimately may prove an efficient
and desirable alternative vector to viruses.
confocal microscopy and fluorescent spectroscopy,
the UB scientists tracked optically in real-time the
process known as transfection, including the delivery
of genes into cells, the uptake of genes by the nucleus
and their expression.
have shown that using photonics, the gene-therapy
transfer can be monitored, tracking how the nanoparticle
penetrates the cell and releases its DNA in the nucleus,"
explained Paras N. Prasad, executive director of the
UB Institute for Lasers, Photonics and Biophotonics,
SUNY Distinguished Professor in the Department of
Chemistry in the College of Arts and Sciences, and
a co-author of the paper.
the fluorescent protein was produced in the cell,
we knew transfection had occurred," he said.
work is important in light of the difficulties that
have plagued gene-therapy human trials in recent years,
including some fatalities that may have resulted from
the use of viral vectors.
delivery of the desired gene and substantial release
inside the cell is the major hurdle in gene therapy,"
explained Dhruba J. Bharali, a coauthor and postdoctoral
researcher in the Department of Chemistry and the
Institute for Lasers, Photonics and Biophotonics,
where the work was done.
have been used as efficient delivery vectors due to
their ability to penetrate cells, but there is the
chance they can revert back to 'wild' type,"
nonviral vectors are safer, he noted that it is much
more difficult to get them into cells and then to
achieve the release of DNA once they do penetrate
advantage of the UB team's approach, he explained,
is that unlike most other nonviral vectors, the DNA-nanoparticle
complex releases its DNA before it can be destroyed
by the cell's defense system, boosting transfection
scientists also were able to use photonic methods
to provide an unprecedented look at how transfection
occurs—from the efficient uptake of nanoparticles
in the cytoplasm to their delivery of DNA to the nucleus.
gene-delivery vehicle—either viral or nonviral—has
ever been tracked in the cell before," explained
Tymish Y. Ohulchanskyy, the third coauthor and postdoctoral
research scholar at the institute. "By using
our photonics approach, we can track gene delivery
step by step to optimize efficiency," he said.
research team makes its nanoparticles from a new class
of materials: hybrid, organically modified silicas
structure and composition of these hybrid ORMOSILs
yield the flexibility to build an extensive library
of tailored nanoparticles for efficiently targeting
gene therapy into different tissues and cell types,"
researchers are collaborating on in vivo studies with
colleagues from the UB School of Medicine and Biomedical
Sciences to use their novel nanoparticles to transfect
neuronal cells in the brains of mice.
research was supported by the U.S. Air Force through
its Defense University Research Initiative on Nanotechnology