Nano World: A nano DNA-delivery system

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http://www.wpherald.com/storyview.php?StoryID=20050726-122809-7406r

By Q. Choi

United Press International

Published July 26, 2005

Scientists have used silica nanoparticles loaded with DNA to deliver

genes safely into mouse brains, a technique that could lead to gene

therapies able to repair cells more safely and effectively than

current methods, which rely on viral vectors.

Gene therapy seeks to transport genes into the body to treat

disorders such as sickle cell anemia, cystic fibrosis, muscular

dystrophy and hemophilia by supplementing unhealthy mutant genes with

therapeutic proteins. With conventional viral-vector gene therapy, the

body's immune system often reacts and seeks to destroy the transported

genes, rendering them ineffective. Moreover, the viral carriers may

damage chromosomes when they insert genes.

Though the therapy has been used successfully to treat a condition

called X-linked severe combined immunodeficiency and has restored the

immune systems of at least 17 children, three children receiving the

therapy developed leukemia.

Paras Prasad, a physical chemist and executive director of the

University of Buffalo Institute for Lasers, Photonics and Biophotonics

in New York, has created silica particles roughly 30 nanometers in

diameter as non-viral gene-therapy delivery mechanisms. The synthesis

of these nanoparticles, led by University of Buffalo chemist Dhruba

Bharali, involves coating their surfaces with organic molecules that

bind to genetic payloads, protecting the delicate DNA from enzymatic

digestion.

" Non-viral vectors are attractive in terms of low cost,

non-infectivity, absence of host response, good patient compliance,

well-defined characteristics and possibility of repeated clinical

administration, " Prasad told UPI's Nano World.

Prasad, along with microbiologist Jim Bergey, neuroscientist

Michal Stachowiak and colleagues, experimented on mouse brains with

nanoparticles bearing genes for a fluorescent green protein and a

molecule bearing the complicated name, nucleus-targeting fibroblast

growth factor receptor type 1. This molecule is linked to the

development of brain cells, and controlling their proliferation could

help treat damage from stroke, Parkinson's disease and Alzheimer's

disease.

After injecting silica nanoparticles into the substantia nigra

pars compacta, or SNc -- a brain region that degenerates in

Parkinson's disease -- the resulting green fluorescent brain cells

revealed that the nanoparticles had delivered their payloads. The

nanoparticles affected more than one-third of the targeted cells -- a

result equal to or greater than the most effective existing viral

delivery systems, Prasad said. No mice showed adverse side effects one

month after the injections.

The findings appear online this week in the Proceedings of the

National Academy of Sciences.

" This is an important and exciting first demonstration that silica

nanoparticles, or other materials with properties similar to silica

nanoparticles, can be used for gene therapy -- maybe even for gene

therapy of serious human diseases such as Parkinson's, " Mark Saltzman,

a biomedical engineer at Yale University, told Nano World. Other

nanoparticles made of biodegradable polymers also could serve in gene

therapy, he added.

Prasad said his team added fluorescent components to help track

the nanoparticles, as well as the proteins that latch onto specific

cells of interest. He cautioned that the long-term effects of these

nanoparticles need further study before any therapeutic use could be

attempted.

" I would say that it is possible, with enough money and talented

people, to develop this technology for use in cancer-related

applications within five years or so, " Saltzman said. " Application for

Parkinson's disease is likely to take much, much longer -- say 15 years. "

Copyright © 2005 News World Communications, Inc. All rights reserved.