NEW YORK (Reuters Health) - A new study using a mouse model of rheumatoid arthritis (RA) shows electroporation can be used to deliver small interfering RNA (siRNA) into joint tissue and produce therapeutic effects.
“Taken together, these results offer promise regarding the use of electroporated siRNA as a new strategy for therapeutic intervention in RA,” Dr. Raymond M. Schiffelers of Utrecht University in the Netherlands and colleagues write.
Electroporation is currently used in the clinic to deliver genes or bleomycin to cancer patients, Dr. Schiffelers told Reuters Health. Using the technology in RA therapy would simply require developing an electroporator that could transfect in and around joints, he added.
SiRNA are short double-stranded RNA molecules introduced into the cytoplasm to block gene expression by selectively shutting down expression of messenger RNA, a process known as RNA interference, Dr. Schiffelers and colleagues note in their report in the April issue of Arthritis & Rheumatism.
While siRNA shows therapeutic promise for a number of illnesses, including RA, it is a large and highly charged molecule that requires a special delivery approach to reach the interior of a cell.
The researchers used electroporation to deliver siRNA to joint tissue in mice with collagen-induced arthritis. They first performed proof-of-principle in vitro and in vivo tests with luciferase-specific siRNA and siRNA targeted against enhanced green fluorescent protein (siRNA-EGFP). Both showed that the activity of the siRNA was specific and local.
Next the researchers tested siRNA targeted to murine tumor necrosis alpha in animals with collagen-induced arthritis. The animals were given anti-TNF alpha siRNA along with electroporation; siRNA-EGFP plus electroporation; electroporation with saline solution; or anti-TNF-alpha siRNA without electroporation.
Anti-inflammatory activity was only seen with the TNF-alpha blocking siRNA given along with electroporation. The findings show that siRNA requires electroporation to have a silencing effect on joint tissue and does not affect genes beyond the joint.
“One of the additional advantages of using siRNA would be that you could target many different factors at once...by simply changing the sequence of the siRNA to target the mRNA of choice,” Dr. Schiffelers added.
Source: Arthritis Rheum 2005;52:1314-1318. [ Google search on this article ]
MeSH Headings:Animal Diseases: Biological Therapy: Disease Models, Animal: Esterases: Genetic Engineering: Genetic Techniques: Investigative Techniques: Ribonucleases: Therapeutics: Gene Therapy: Drugs, Investigational: Analytical, Diagnostic and Therapeutic Techniques and Equipment: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
