분자유전학실험실 (단국대학교 분자생물학과)



 이성욱 ( 2007-05-22 10:21:12 , Hit : 4018
 New gene therapy targets cholesterol

First there was gene therapy, then came RNA interference. Now the latest technology promising to regulate gene expression has been used therapeutically for the first time - if only in mice - to cut cholesterol levels. The technique, termed microRNA (miRNA) inhibition, has also been used to stop hepatitis C infecting cells.

It is related to earlier forms of RNA interference (RNAi), such as siRNA - in which a double-stranded "short interfering RNA" is used to intercept and destroy messenger RNA (mRNA) before it can be translated into protein. But unlike siRNA, which works to silence genes, miRNA inhibition increases the amount of protein that gets produced by intercepting the molecules - miRNAs - that normally act as a brake on mRNA translation (see Diagram).

MicroRNAs are thought to control up to 30 per cent of all gene activity, with one type responsible for directing the expression of whole networks of genes, rather than just single genes. Changes in the expression of miRNAs have been implicated in cancer and other diseases, including viral infections (New Scientist, 11 June 2005, p 18).

RNAi-based therapies have so far failed to take off because of the difficulty of getting the therapeutic molecules into target cells, but according to work conducted at Santaris Pharma in Hørsholm, Denmark, miRNA-inhibiting drugs appear to be readily absorbed by cells without the need for a separate delivery vehicle. The company has been targeting an miRNA called miR-122, which is thought to regulate up to 450 genes, around 100 of which are involved in cholesterol and lipid metabolism. It is only expressed in liver cells.

Santaris created short, single-stranded RNA molecules designed to bind specifically to miR-122 and injected them into mice. This miRNA inhibitor, or antimiR, was readily taken up by liver cells and lowered cholesterol by up to 35 per cent. Inhibiting miR-122 also seems to protect the liver against hepatitis C infection, tests on cell cultures suggest.

"Nobody quite knows why, but if you don't have miR-122, the cell no longer supports viral replication," says Keith McCullagh of Santaris. "As a drug, [antimiR-122] has the potential for hepatitis C and cholesterol reduction."

"The great thing about it is that it's a graded response," adds Troels Koch, also of Santaris, who presented the results at the RNAi 2007 meeting in Boston, Massachusetts, earlier this month. This means that the more antimiR that was given, the greater the cholesterol-lowering effect.

This is another difference from siRNA therapy, says Johannes Fruehauf, an RNAi researcher at the Beth Israel Deaconess Medical Center in Boston, since once siRNA molecules are introduced into the cell and activated they can destroy a whole series of mRNA transcripts from a particular gene, resulting in almost complete gene silencing. In contrast, each miRNA acts on just one mRNA strand. "miRNA inhibition seems to be a much softer tool," Fruehauf says.

As for why miRNA inhibitors should find it so much easier to cross cell membranes and to exert their effect, Koch offers several explanations. For a start they are single-stranded and shorter than most siRNAs. "The smaller the molecule the easier it gets across," he says. Most siRNA therapies being developed rely on a delivery vehicle such as a liposome capsule to get them across the cell membrane, but antimiR-122 was simply injected into the mice in saline solution.

Furthermore, the nucleotide structure of antimiR has been modified to make it more stable. That means it lasts longer in the body, and also ensures it binds to miRNA more strongly than it would otherwise, says Koch.

Some researchers question the wisdom of developing miRNA inhibitors before we completely understand how the miRNA regulatory system works...








1127   마이크로 RNA가 면역계에 미치는 영향  이성욱 2007/04/30 4906
1126   DNA 수복의 오류가 헌팅턴병을 초래  관리자 2007/05/01 4365
1125   알츠하이머에 효과적인 신규 물질  관리자 2007/05/01 4115
1124   죽음에 관한 기존 학설 깨졌다<뉴스위크>  관리자 2007/05/03 3811
1123   췌장암 진단과 치료에 도움을 주는 microRNA 연구  이성욱 2007/05/03 5255
1122   류마티스 관절염에 효과를 보인 녹차성분 EGCG  이성욱 2007/05/03 5367
1121   유방암 치료에 획기적인 병용치료법  이성욱 2007/05/10 5561
1120   마이크로RNA 유전자 발현 억제 기전 규명  이성욱 2007/05/18 4866
1119   p53: 양면의 날을 가진 검(劍)  이성욱 2007/05/18 4596
  New gene therapy targets cholesterol  이성욱 2007/05/22 4018
1117   인간과 헤르페스바이러스는 공생관계?  이성욱 2007/05/23 7335
1116   방사선을 먹는 진균 발견  이성욱 2007/05/25 7008
1115   1형 당뇨병 백신, 동물 실험에서 효과  이성욱 2007/05/28 4798
1114   기억과 학습에도 영향을 주는 알츠하이머 관련 유전자  관리자 2007/05/31 4137
1113   마리화나 중독을 차단하는 식물 추출물  관리자 2007/05/31 4309
1112   나노입자를 이용한 선택적 전립선 암 치료 연구  관리자 2007/06/01 4317
1111   제대혈 줄기세포에서 인슐린을 생산  관리자 2007/06/01 3885
1110   Gene therapy 'hope' on impotence  이성욱 2007/06/04 5114
1109   Genetically Modified Stem Cells May Have Therapeutic Application to X-SCID  이성욱 2007/06/04 4555
1108   장기기억을 향상시키는 항암제  관리자 2007/06/08 4619

[1][2][3][4][5][6][7] 8 [9][10]..[64] [다음 10개]
 

Copyright 1999-2024 Zeroboard / skin by ROBIN