BAKTEERI-INFEKTIOIDEN UUSI HOITOMENETELMÄ

[Bb]

Lähettäjä: Soijuv Lähetetty: 12.9.2005 8:17

Tutkijoiden mukaan geenien "vaimennustekniikalla " saatetaan tulevaisuudessa kyetä hoitamaan vaikeita bakteerien aiheuttamia infektioita:


Gene Silencing Technique Successfully Treats Bacterial Infection

By Will Boggs, MD

NEW YORK (Reuters Health) Aug 26 - Gene silencing with antisense peptide nucleic acid (PNA) oligomers inhibits bacterial growth and prevents fatal infection in a mouse model, according to a report by researchers based in Houston, Texas.

"The gene silencing approach targets the fundamental genetic mechanisms that control the very existence of the bacteria," Dr. Yin Chen from Cytogenix, Inc., told Reuters Health. "It is very specific and can be refined to be effective only against pathogenic species."

Dr. Chen and associates investigated the ability of the antisense PNA-peptide conjugate to inhibit bacterial growth in vivo and to rescue mice from intraperitoneal infection.

The fatty acid biosynthesis protein ACP was targeted by the antisense PNA, and the peptide was used to facilitate passage of the PNA through the bacterial outer membrane, the authors explain in their report in the August issue of Antimicrobial Agents and Chemotherapy.

Antisense PNA targeting the ACP gene significantly inhibited bacterial growth in a time- and concentration-dependent fashion, the report indicates.

All mice treated with PNA after intraperitoneal injection with 70% of the lethal dose of SM101 bacteria survived and completely eradicated the bacteria, the authors report, whereas 62.5% of the untreated mice died within 48 hours of injection and demonstrated high levels of bacteria in serum at 24 hours postinfection.

Treatment with PNA also led to significant reductions in serum IL-6 and IL-12 and, at a higher dose, in TNF-alpha. The PNA-peptide conjugate (but not PNA alone) markedly inhibited growth of wild-type E. coli in vitro, the researchers note.

All mice infected with these E. coli and treated with 500 nmol PNA-peptide conjugate survived, the results indicate. Mice treated with a lower dose of PNA-peptide conjugate showed a survival benefit over controls, 90% of which died within 48 hours of infection.

"The results presented here demonstrate that antisense oligodeoxynucleotides, when conjugated to membrane-permeabilizing peptides, can effectively inhibit bacterial growth in vivo and may be useful as therapeutic agents," the authors conclude.

"Although years away from clinical use, this class of compounds has great promise because our gene silencing technique is species or strain specific depending on the nature of the organism," Dr. Chen said. "For example, we have developed several compounds with activity against all strains of S. aureus, including several strains of MRSA."

Antimicrob Agents Chemother 2005;49:3203-3207.

Reuters Health Information 2005. © 2005 Reuters Ltd.
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.

Shortcut to: http://www.medscape.com/viewarticle/511670?src=mp