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Genome Technology s Peer Review: A Weekly Forum of Recently Published Journal Articles: Jun 7, 2005

NEW YORK, June 7 (GenomeWeb News) - Following is a description of two recently published research papers recommended by a scientist involved in integrated biology. The recommender, Roderick Beijersbergen, is in the Division of Molecular Carcinogenesis at The Netherlands Cancer Institute.

 

For a complete list of recommended papers, read Genome Technology, a GenomeWeb News sister publication.


"Silencing mutant SOD1 using RNAi protects against neurodegeneration and extends survival in an ALS model." Ralph GS, Radcliffe P, Day DM, Carthy JM, Leroux MA, Lee DCP, Wong LF, Bilsland LG, Greensmith L, Kingsman SM, Mitrophanous KA, Mazarakis ND, and Azzouz M, Nature Medicine 11, 429 - 433 (2005).

 

The paper by Ralph et al. describes the use of an EIAV based lentiviral vector to direct the expression of a shRNA targeting the mutant form of human SOD1 (SOD1G93A). Upon intramuscular injection and retrograde transport the authors show decreased expression levels of SOD1 in the ventral horn of the lumbar spinal cord and, as a consequence, a delayed onset of motor symptoms from less than a 100 to over 200 days. As striking is the increased survival of these animals from around 130 days to more than 220 days.

 

This study elegantly describes the use of a vector-based RNAi in a clinical setting, and it shows that directly using the shRNA vector to target the specific factor underlying the disease can have great therapeutic benefits, says Roderick Beijersbergen at the Netherlands Cancer Institute. Newly identified gene targets for a specific disease can potentially be targeted by the very identical shRNA used to find the particular gene, and more importantly, previously identified genes in disease can be used in the same manner, he adds. One concern is the method of delivery, but the use of a non-invasive method used in this study boosts the expectations for the use of vector based RNAi in the clinic, he says.

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