August 1 is RNA Day. BioSpace takes a look at recent breakthroughs in RNA therapeutics, and the vast potential of the “vital biological molecule.”
August 1 has been designated as annual RNA Day, what the University of Lethbridge calls “a celebration of the vital biological molecule, ribonuclear acid.”
Officially recognized as a molecule separate from DNA in the 1930s, RNA has a structural similarity to its biological cousin but is usually single-stranded. It has a number of functions, encompassed by messenger RNA (mRNA), transfer RNA (tRNA) and ribosomal RNA (rRNA). mRNA carries genetic codes from the DNA to the nucleus to ribosomes, where proteins are translated. Ribosomes are made up of rRNA and protein.
Messanger RNA provides the instruction manual for sequences that direct the ribosome to bind in a specific place, denote the start and the end of the protein-coding region and affect modification of the messenger RNA molecule itself. Three nucleotides, adenine (A), uracil (U) and guanine (G), comprise the start signal - hence the celebration on the start date of August.
In the spirit of the day, let’s look at some recent breakthroughs in RNA therapeutics, and anticipate what is still to come.
Pushing mRNA Beyond Infectious Disease
Pfizer, BioNTech and Moderna are all noted for being the first companies to ever have mRNA vaccines approved, in this case, for the prevention of COVID-19. Moderna and BioNTech, in particular, are actively involved in developing more mRNA-based vaccines against other infectious diseases. Moderna has mRNA programs assessing vaccines for cytomegalovirus, HSV, Zika, Nipah, RSV and flu, among other viruses. However, both Moderna and BioNTech are working to push mRNA therapeutics into non-infectious disease indications. Moderna has mRNA programs for autoimmune disorders and cancer, including a personalized cancer vaccine (mRNA-4157), a KRAS vaccine (mRNA-5671) and a checkpoint vaccine (mRNA-4359).
In April, BioNTech presented data from the first-in-human Phase I/II trial of its CAR-T cell therapy, BNT211, in patients with advanced solid tumors. The therapy is made up of two drug products: an autologous CAR-T cell therapy that targets the oncofetal antigen Claudin-6 (CLDN6) and a CLDN6-encoding CAR-T cell amplifying RNA vaccine (CARVac), which uses the company’s mRNA-lipoplex technology.
Interestingly, on Friday, AstraZeneca reported that it had abandoned an mRNA therapy, AZD8601, on which it had partnered with Moderna. The drug candidate, AZD8601, is an mRNA therapy that encodes vascular endothelial growth factor (VEGF-A). At this time, Moderna appears to still be working on the drug.
Circular RNA Offers Unique Stability
In May, Orna Therapeutics announced the first data from its lead program, validating its technology and lipid nanoparticle (LNP) delivery platform. Orna is creating O-shaped RNA therapies to treat cancer, autoimmune and genetic diseases. Because the RNA is circular, it is more stable than typical linear RNA. The data presented from Orna’s lead isCAR program demonstrated tumor suppression and eradication in a NALM6 leukemia mouse model.
“We were hoping for a blip, like if we hammered this, maybe that would give us something to work with,” Orna CEO Tom Barnes, Ph.D. told BioSpace. “But in our very first experiment, we eradicated the tumor.”
Alnylam’s RNAi Portfolio
Alnylam Pharmaceuticals focuses on RNA interference (RNAi), where small pieces of RNA can shut down protein translation by binding to the mRNA that codes for the proteins. On July 28, the company offered up its second-quarter financials, reporting global net product revenues of $214 million for Onpattro, Givlaari and Oxluma, all developed with Alnylam’s RNAi platform. In June, the company received approval from the FDA for Amvuttra (vutrisiran) for the treatment of polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.
Alnylam CEO Yvonne Greenstreet said, “We’re pleased with our second quarter results which delivered strong growth in both patient demand and product revenues. A notable achievement in the quarter was the recent approval of Amvuttra, which becomes our fifth RNAi therapeutic approved in under four years and marks our continued progress in building a multi-product TTR franchise.”
More mRNA Action
In June, CureVac, which is developing mRNA therapies, acquired Frame Cancer Therapeutics in order to augment its cancer vaccine portfolio. Frame focuses on advanced genomics and bioinformatics to identify neoantigens across various cancer types.
“The addition of Frame’s technology and talent to CureVac’s oncology research complements our ability to identify and validate promising neoantigens for our mRNA cancer vaccine programs,” Franz-Werner Haas, CEO of CureVac said at the time.
Hans-Joachim Wieden, Ph.D., founding director of the Alberta RNA Research and Training institute at the University of Lethbridge shared his thoughts on RNA.
“RNA will play a critical role in the new age of biotechnology — the rational design and engineering of biomolecular-based systems and molecular machines,” he stated. “The role of RNA in new and upcoming disruptive technology has been foreshadowed by the recent commercial successes of the CRISPR gene-editing platform and the emergence of RNA-based therapeutics and pesticides.”
Happy RNA Day from BioSpace!
