Stories about: RNA

News Note: A fresh perspective on RNA with big implications for drug development 

RNA-based drugs are the future of therapeuticsRibonucleic acid, or RNA, has long been underappreciated for its role in gene expression. Until recent years, RNA has been thought of merely as a messenger, shuttling DNA’s instructions to the genetic machinery that synthesizes proteins.

But new discoveries of RNA functions, modifications and its ability to transcribe sections of the genome that were previously considered “junk DNA” has led to the discovery of a huge number of new druggable targets.

These new insights into RNA’s complex purposes have largely been uncovered through ever-increasingly sensitive and affordable sequencing methods. As a result, RNA-based drugs now stand to greatly extend our ability to treat diseases beyond the scope of what’s possible with small molecules and biologics.

Although several RND-based drug approaches have already been established, some barriers still prevent these strategies from working broadly. In a review paper for Nature Structural and Molecular Biology, Judy Lieberman, MD, PhD, of the Program in Cellular and Molecular Medicine of Boston Children’s Hospital, lays out where RNA-based drug development currently stands.

Lieberman, who has helped pioneer the RNA-based drug revolution herself, was the first scientist to show in an animal disease model that small, double-stranded RNAs could be used as drugs and leveraged to knock down genes in cells.

Read Lieberman’s review: “Tapping the RNA world for therapeutics.”

Read Full Story | Leave a Comment

Science Seen: Tackling S. aureus by eavesdropping on infections

S. aureus vaccine messenger RNA transcriptome
This messenger RNA ‘heat map,’ generated from 50 patient samples, shows potential target proteins for a more effective S. aureus vaccine. The color scale indicates the magnitude of the transcription level, with red highest.

Staphylococcus aureus causes 11,000 deaths annually in the U.S. alone and is frequently antibiotic-resistant. It’s a leading cause of pneumonia, bloodstream infections, bone/joint infections and surgical site infections and the #1 cause of skin and soft tissue infections. Efforts to develop an S. aureus vaccine have so far failed: the vaccines don’t seem to be capturing the right ingredients to make people immune.

Kristin Moffitt, MD, in Boston Children’s Hospital’s Division of Infectious Diseases, took a step back and asked: “What proteins does S. aureus need to make to establish infection?” The answer, she reasoned, could point to new antigens to include in a vaccine.

The above image shows an early result from Moffitt’s investigation. It’s a “heat map” of the messenger RNA signature — a snapshot of the proteins S. aureus is potentially up-regulating during infection.

Read Full Story | Leave a Comment

Big things from small places: Modified RNAs eyed as a way to make new drugs

A technology from a small research institute, originally developed as a safer way to make embryonic-like stem cells, just hooked a very large fish. As The New York Times reported yesterday, pharma giant AstraZeneca is betting at least $240 million that this technology could be the source of a variety of new drugs—drugs that spur the body itself to make what it needs.

In 2010, the lab of Derrick Rossi at the Immune Disease Institute, which is now the Program in Cellular and Molecular Medicine at Boston Children’s Hospital, reported that they could reprogram ordinary cells into pluripotent stem cells by simply injecting them with messenger RNAs. The mRNAs reprogrammed the cells up to 100 percent more efficiently than other techniques, and did so without becoming part of the cell’s genome, greatly reducing concerns about cancer associated with other methods.

Key to the discovery were the chemical modifications made to the mRNAs so that cells wouldn’t “see” them as viruses and attack them. This video and this article describe the modified mRNA technique, also described in Cell Stem Cell:

Read Full Story | Leave a Comment