Nature Biotechnology：SiRNA New Method of Drug Delivery

Researchers at the University of California, San Diego Medical College have successfully developed an effective method for transporting small interfering RNA (siRNA) into primarycells. They believe that in the future, the technology will be able to target drug delivery to the patient's disease site and malignant tumors. The related research was published in the online edition of Nature Biotechnology on the 17th.

Small interfering RNA (SIRNA), also known as short interfering RNA, is a kind of double-stranded RNA molecule with many biological functions, ranging from 20 to 25 nucleotides in length. SiRNA is involved in RNA interference (RNAi) pathway and interferes with the expression of specific genes. Steven Doddy, professor of cell and molecular medicine at the Medical College of San Diego, said: "RNA interference has incredible potential in controlling and treating cancer. Although there is still a long way to go from practical application, we have developed a technology that can fully deliver siRNA drugs into primitive and carcinogenic cells.

Over the years, Dodi has been studying the ability to shut down genes using siRNA. However, due to the size and negative charge of siRNA, it is difficult for siRNA to enter cells quickly, so how to transport them is always a problem. After the discovery of the ability of PTD protein fragments to penetrate cell membranes, Dodi and his colleagues saw the potential of using PTD protein to deliver siRNA into cancer cells. At the beginning of the study, PTD was linked to tumor suppressor proteins to produce more than 50 fusion proteins.

Because siRNA has a strong negative charge and PDA has a positive charge, their aggregates cannot enter cells, so simply carrying siRNA to PTD does not work. The researchers constructed the fusion protein of PTD and double-stranded RNA-binding domain (DRBD) and named it PTD-DRBD. The fusion protein masks the negative electricity of siRNA, and as a result, it can enter cells and send siRNA into the cytoplasm, promoting the release of messenger ribonucleic acid (RNA) from genes and shutting down oncogenic genes.

Dodi's team also acquired the ability to introduce genes that shut down proteins into most cells, such as T cells, endothelial cells and human embryonic stem cells. More importantly, they found that fusion proteins were not toxic to cells or innate immune responses, and transcriptional deviations rarely occurred.

The main problem with current cancer therapies is that if cancer recurs, the original therapies will not be able to continue to be used. The reason is that genetic mutations occur in the tumors, which avoid the attack of the original drugs. Because synthetic siRNA is specifically designed to absorb single mutation genes and genomic mutations, Doddy said, it can easily and quickly change and continue to use PTD-DRBD fusion protein into cells.