실질적인 유전자 요법(gene therapy)을 만들어내기 위한 단계에 있어서, 연구자들은 유전자의 RNA 복제물을 표적으로 하는 한 방법을 사용함으로 인하여, 포낭 섬유증(cystic fibrosis)과 연관되어 있는 유전자를 부분적으로 고치는데 성공하게 되었다. 문제의 그 유전자는 세포막을 가로지르는 염류 이온들의 흐름을 억제하는 CFTR 단백질을 암호화한다. 이 유전자는 낭포 섬유증을 앓는 환자들에게 결함되어 있을 수도 있다.
Gene Therapy for Cystic Fibrosis
In a step toward making gene therapy a reality, researchers have succeeded in partially repairing a cystic fibrosis-associated gene using an approach that targets the RNA copy of the gene. The gene in question encodes a protein (known as the cystic fibrosis transmembrane conductance regulator, or CFTR) that controls the flow of chloride ions across cell membranes; this gene can be defective in people with cystic fibrosis.
Working on cystic fibrosis tissue that had been transplanted into mice, the researchers have restored chloride ion conductance to 22% of that seen in normal cells-a level that should alleviate disease symptoms if it can be achieved in individuals with cystic fibrosis.
The goal of gene therapy is to substitute "normal" genes for defective genes associated with disease. Such genes give rise to faulty proteins through a series of steps, and gene therapy researchers can try to correct the genetic defect at any of these steps.
In the January 2002 issue of Nature Biotechnology, John Engelhardt and his team focused on the point at which an RNA copy of the gene is processed by a cellular machine that splices out long stretches of the molecule to create a mature RNA, which then goes on to direct the production of a protein. The researchers used an adenovirus to carry the correct genetic sequence into cells, where it was spliced into the mature RNA. This "corrected" RNA was then used by the cells to synthesize a normal version of the CFTR protein.
Unlike many more traditional forms of gene therapy, in which a "normal" gene sequence is introduced into cells to counteract the deleterious effects of a defective gene, Engelhardt's approach has the advantages of both correcting the genetic defect and ensuring that the "corrected" RNA is expressed at levels appropriate to ensure attaining airway function closer to that seen in healthy individuals. Although the results are very encouraging, modifications will be required before this RNA-targeted approach can be tested on people with cystic fibrosis. For example, an alternative virus carrier will be needed, because adenovirus does not readily enter human lung cells.
출처: http://bio.com/newsfeatures/newsfeatures_research.jhtml?action=view&contentItem=11128033&Page=1
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