High-speed transport for miRNA
Courier for the "switch" of genes
STRF.ruResearchers from Alnylam Pharmaceuticals Inc. and the Massachusetts Institute of Technology (MTI) have created a whole class of new lipid-like carriers (lipidoid) that increase the efficiency of delivery of small interfering RNAs (miRNAs, siRNAs) by hundreds of times.
Currently, the created transport particles are being tested on model animals with genetically determined diseases.
If positive results are obtained, lipid–like particles will be able to solve one of the most urgent problems of gene therapy - how to deliver an agent (in this case, miRNA) regulating the work of genes into the cell. This technology is the basis of the RNA Interference method (RNAi).
It is much easier to use lipid-like compounds of a new type for miRNA transport compared to the previous class of liposomes. During synthesis, lipid-like particles together with miRNA self-organize into nanoparticles with high penetrating power. This reduces the number of synthesis and purification stages, and most importantly, increases the number of combinatorial variations.
During the joint work of Alnylam and MTI, a library of more than 1,200 lipid-like miRNA carriers was created. After careful selection and testing on rats, mice and primates, scientists have identified 126 structures with the maximum therapeutic effect and the least toxicity.
12 carriers were tested on cell cultures, which were able to deliver miRNA in quantities sufficient to "turn off" the luciferase gene. Luciferase and the effect of bioluminescence are widely used in biological and medical research. The amount of luciferase in the cell, and hence the level of luminescence, depends on the activity of the luciferase gene. In this study, the effectiveness of miRNA delivery is determined by the complete cessation of the synthesis of luminescent protein in 80 percent of cells.
One of the synthesized carriers showed high efficiency in experiments to regulate the expression of the Factor VII gene (one of the blood clotting factors) in liver cells. The effective therapeutic dose was 0.01 mcg/kg of weight. In a series of experiments to "turn off" the transthyretin gene (a protein that provides the transport of thyroxine and retinol; associated with diseases such as senile systemic amyloidosis, familial amyloid polyneuropathy, familial amyloid cardiomyopathy), the effective therapeutic dose was 0.03 mcg/kg.
Given the high efficiency, experts suggest that these transport particles will be able to deliver several active agents into the cell without side toxic effects.
The results of the work are published in the Proceedings of the National Academy of Sciences (Kevin T. Love et al., Lipid-like materials for low-dose, in vivo gene silencing).
Portal "Eternal youth" http://vechnayamolodost.ru18.01.2010