As more of the human genome is identified and characterized, new frontiers open for therapeutics. “The RNA interference (RNAi) research space continues to explode,” explains Susan Magdaleno, Ph.D., senior manager of scientists, RNAi technologies R&D, Life Technologies. “We are actually expanding into new content. Part of it is a result of the exploding data coming from next-gen sequencing—when you look at that content, it’s not messenger RNA. There are a lot of RNAs there that have yet to be characterized.”
“RNAi is a fast moving field—even incremental advances can result in high-profile publications,” agrees Paloma Giangrande, Ph.D., assistant professor, department of internal medicine, University of Iowa. “The promise of RNAi gets people excited, and any progress gets RNAi closer to the clinic.”
At CHI’s “RNA Interference: From Tools to Therapies” conference to be held in San Francisco next month, some of the latest tools and best practices captured from labs across academia and pharma will be described.
A noncoding RNA (ncRNA) is a functional RNA molecule that is not translated into a protein. ncRNA genes include highly abundant and functionally important RNAs such as transfer RNA (tRNA) and ribosomal RNA (rRNA). The number of ncRNAs encoded within the human genome is unknown, but Dr. Magdaleno says that her group’s efforts are to bring some functional analysis to ncRNA. “We’re starting to link ncRNA to disease, and it’s starting to grab the attention of investigators.”
ncRNA opens up novel targets for therapeutics. “Not all disease can be explained by changes in proteins, and there is only so much you can discover in proteins,” she adds. “Epigenetics is another area that is being greatly explored. ncRNAs might be influencing regulation at the epigenetic levels. The trick is to develop the tools that will allow robust functional analysis.”
Life Technologies developed a suite of integrated tools and workflows to discover, validate, and knock-down ncRNA to accelerate understanding of the function of ncRNA in the cell. At the conference, Dr. Magdaleno will describe requirements for using siRNAs to knock-down ncRNA and will highlight the application of siRNAs to investigate ncRNA function in regulating mitosis and apoptosis in normal and cancer cells.
“ncRNAs are not as well-characterized as messenger RNAs and many are not as abundantly expressed as messenger RNAs—low abundance is a challenge; many are only present under specific conditions. We don’t know why they are there, what happens to them, and whether we can develop therapeutic solutions based on ncRNA.”
Dr. Magdaleno’s group develops best practices for studying ncRNAs, which is not without challenges. “The ones we are focusing on are greater than 180 nucleotides. These are not highly characterized, there is no single fundamental source database of ncRNAs, nor is there an agreed upon definition of an ncRNA database. We are early in this field, but it’s important to determine functionality of these RNA species. We have the technology, but workflows still need to be figured out.”