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The RNAi Revolution Marches On

 
  March, 29 2006 9:23
your information resource in human molecular genetics
 
     
Scientists have taken an important step towards a new class of drug treatment that harnesses the RNA interference pathway. Reported online by Nature, a new study shows for the first time that systemic administration of small interfering RNA (siRNA) can be used in non-human primates to silence a disease-causing gene that is otherwise inaccessible to targeting with conventional therapies.

Tracy Zimmermann and colleagues exploit a normal cellular process, RNA interference (RNAi), to suppress the expression of a gene associated with heart disease. The authors have previously used a mouse model system, but here they study the effects of RNAi therapy in cynomolgus monkeys (Macaca fascicularis). They gave the monkeys a single injection of siRNA targeted against the gene for apolipoprotein B (ApoB), a protein involved in the secretion and assembly of low-density lipoprotein (LDL), the 'bad' cholesterol. Within 48 hours, the level of gene silencing exceeded 90%, leading to significant reductions in ApoB protein, serum cholesterol and LDL levels. The effect was also persistent, with ApoB gene expression being substantially reduced for at least 11 days.

This research has implications for diseases associated with high cholesterol levels, such as coronary heart disease, and continues to highlight RNAi as a promising therapeutic approach.

Author contact:

Tracy Zimmermann (Alnylam Pharmaceuticals, Cambridge, MA, USA)
E-mail: tzimmermann@alnylam.com

(C) Nature press release.


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