A fast route to find reagents for silencing disruptive genes has been developed by scientists in the UK.

A fast route to finding reagents for silencing disruptive genes

Michael Gait from the Laboratory of Molecular Biology, Cambridge, and colleagues have developed a rapid method for determining the stability of small interfering RNA (siRNA) in blood serum. Tailor-made siRNA molecules that can silence (switch off) therapeutically important genes are a hot topic of research, said Gait, but the more significant challenge is delivering these molecules into the human body undamaged. RNA can be degraded by proteins in the blood, so quick methods to determine siRNA stability in blood serum are essential, he said. 

Gait's method uses mass spectrometry to detect degradation fragments of synthetic siRNAs that have been exposed to blood serum. These can then be used to identify the most vulnerable cleavage sites in the molecules, said Gait. 

Gait said that the technique could become a first choice for establishing the most serum-stable siRNA sequences for use in vivo. John McLean, an expert in mass spectrometry for chemical biology from Vanderbilt University, Nashville, US, agreed. The method will help direct siRNA tailoring for future therapeutics; it is faster, requires less sample preparation, and gives better results than the assays traditionally used for this purpose, said McLean. 

Nina Athey-Pollard