RNA interference for biopharmaceuticals
Biopharma relies on "turning off" genes
Elena Novoselova, STRF.ru based on the materials of Nature:
Gene silencing predicted to improve drug manufacturingThe more data there is about the possibility of manipulating RNA interference (RNAi) in order to silence genes, the more biotechnological developments based on the mechanism of "turning off" genes for pharmaceuticals appear.
For example, the biotech firm Alnylam Pharmaceuticals (Cambridge, Massachusetts, USA) It already uses short interfering RNA (siRNA) molecules in its R&D developments, the role of which is to regulate the activity of specific genes. Now the company plans to use RNA interference to increase the production of biological products (pharmaceutical proteins, monoclonal antibodies, vaccines). The company has created a special division of Alnylam Biotherapeutics, which will improve the technology and increase the production of drugs in cell cultures.
According to the representative of the company John Maraganor, they managed to decipher the sequence of genes in the cells of the CHO line (ovarian cells of Chinese hamsters), the most widely used for the synthesis of recombinant proteins after preliminary amplification (formation of additional copies of sections of chromosomal DNA) of genes introduced into cells. The use of cells in which the amount of a particular gene is increased several times, allows you to synthesize a larger amount of the desired protein. Using small interfering RNAs specially developed in the laboratory of Alnylam, scientists hope to extend the life cycle of cells of the CHO line, which will allow them to produce more therapeutic protein.
Suppressing the expression of just two genes regulating the mechanism of cell death increases the cell's lifespan by 40 percent. Also in this company, miRNAs were obtained specifically focused on the effect on one gene involved in lactic acid metabolism, which prolongs cell viability in culture by 60 percent. "Using this technology will allow the cell to live longer and work more," said the director of Alnylam.
This approach is used not only by Alnylam to increase the productivity of biopharmaceutical production. Thus, a team of researchers from Singapore's Bioprocessing Technology Institute was able to obtain twice as many synthesized proteins in CHO cell culture by manipulating the interference mechanism. According to one of the leaders of this project, Zhivei Song, the main task now is to develop a technique for using RNA interference on large-scale cell cultures, for example in bioreactors.
According to Derek Ellison, director of the biopharmaceutical company Eden Biodesign (UK): "Tools that increase the productivity of cell culture without changing its qualitative composition are of great interest to biopharma. But first, Alnylam must prove that their method of regulating gene expression does not affect the quality of the synthesized protein."
Bioengineer Su-Chin Wu from the National Tsinghua University (Taiwan) sees no reason for problems with the quality and safety of proteins when using the method of RNA interference in cells of the CHO line. In his review of the prospects and risks of this technology, he cites for confirmation the results of a series of experiments with drugs at the last stage of clinical trials, which were obtained using the RNAi method.
However, Tillman Gerngross from Dartmouth College in Hanover (USA) believes that this technology may not be profitable. In his opinion, the actual production is a small part of the cost of the pharmaceutical product, and it is more promising to use new technologies to increase the quality and effectiveness of the drug, rather than increasing the volume of production.
Portal "Eternal youth" http://vechnayamolodost.ru23.11.2009