BYLINE: Erin Frick

Newswise — ALBANY, N.Y. (Jan 31, 2024) — University at Albany scientist Scott Tenenbaum, founder of UAlbany spinoff company sxRNA Technologies, Inc. (sxRNA Tech), has received $500,000 from the National Institute on Aging, part of the National Institutes of Health, to study how aging brain cells shape the progression of Alzheimer’s disease, and advance RNA technology that could inform new therapeutics to prevent and treat Alzheimer's and related dementias.

The one-year award takes the form of a Small Business Technology Transfer (STTR) grant — a funding mechanism aimed at supporting small businesses engaged in cutting-edge research with high commercialization potential. The grant was awarded to sxRNA Tech, which currently occupies incubator space in NY CREATES' Albany Nanotech Complex, with plans to expand into the RNA Institute in the College of Arts and Sciences. UAlbany is a shareholder in the company.

"We commend the sxRNA team for their efforts in bridging decades of laboratory research with the development of market-ready applications with strong potential for significant public benefits,” said UAlbany’s Thenkurussi (Kesh) Kesavadas, vice president for research and economic development. “Applying sxRNA technology in the exploration and testing of novel drugs for the treatment of various diseases exemplifies the kind of translational research that drives critical advancements in biomedical sciences.”

Advancing sxRNA with STTR

“As brain cells age, some can begin secreting toxic chemicals that harm surrounding cells,” said Professor Tenenbaum, who holds joint appointments in the Department of Nanoscale Science and Engineering in the College of Nanotechnology, Science, and Engineering (CNSE) and the RNA Institute. “These emissions can cause neurons to fire spontaneously or stop firing altogether. This pathology has been found in the brains of people affected by Alzheimer’s disease and is at the center of this research.”

SxRNA Tech builds ribonucleic acid (RNA) “switches,” also called structurally interacting RNAs (sxRNA), which are molecular tools for targeting and stopping harmful cells that cause disease. This new work will focus on senescent (aging) brain cells, but the technology can be used to target any cell type, including applications in vaccine production.

“STTR grants are designed to leverage early-stage technology that comes from a university and is ripe for commercialization but isn’t quite ready to run on its own,” said Tenenbaum. “Our technology, sxRNA, is a good example of that. Pairing university research and product development should enable sxRNA to move more swiftly from lab to market.”

Collaborators on the project include Associate Professor Janet Paluh of CNSE’s Department of Nanoscale Science & Engineering, who develops organoids — groups of cells that function as tiny organs and serve as important tools for studying diseases and developing new treatments, and Andres Melendez, professor and chair of the same department, who is also affiliated with the RNA Institute and is a leading expert on cell senescence.

How sxRNA works

The same basic rules of nucleotide base pairing that we see in DNA are what dictate the structure of an RNA. Altering the nucleotide sequence of an RNA will change the shape of its structure, effectively transforming it into a tool that can be used for a range of biomedical applications.

A focal goal of the project is to develop a molecular “switch” designed to turn off processes in aging brain cells that cause them to emit chemicals that disrupt neuronal functions and trigger symptoms of dementia.

“Whatever kind of cell we want to target will have a particular nucleotide sequence; this genetic signature will guide the RNA structure that we work to produce,” said Tenenbaum.

How does this play out in the lab? The team produces a piece of RNA called the “bait,” which interacts with another piece of RNA that comes from the cell, which is called the “trigger.” When the bait and trigger come together, they fold up into a structure that can do a particular job — like turn on a desired genetic expression, or turn off something harmful.

“We figured out the rules to reverse-design RNA structures based on the genetic sequences that we want to target, and we use an algorithm written by former grad student Frank Doyle to identify sequences that could achieve the proper binding,” said Tenenbaum. “The sequence and RNA structure will be different for each target cell type. For a given application, we'll pick, say, a dozen promising sequences, produce the RNAs, then test them on organoids at the bench to figure out which ones are behaving as they should.”

In this new work, Tenenbaum’s RNA switches will be tested with Paluah’s brain organoids to determine which are effective at stopping senescent brain cells from releasing toxic substances associated with cognitive impairment and dementia.

Commercializing sxRNA

Tenenbaum founded sxRNA Tech several years ago, and with help from UAlbany’s Office for Innovation Development & Commercialization (OIDC), the company has secured three patents for their technology. Tenenbaum attributes the success of the STTR proposal to his team’s collaboration with the SUNY Research Foundation (RF).

Working in close coordination SUNY’s Office of Research, Innovation, and Economic Development, the RF’s Industry and External Affairs team manages a portfolio of programs designed to maximize SUNY’s research, innovation and entrepreneurial capacity and realize the very real and measurable impact it has on the world. SUNY Startup Grant Works, which has a 60% success rate, provided Tenenbaum with professional guidance to perfect his proposal and submit the application.

“Receiving this STTR is a testament to the power of the technology transfer ecosystem that is in place to help SUNY faculty translate their research into a commercial entity, with benefits for the university as well as the broader public,” said Tenenbaum. “Here, we identified a technology that could be commercialized and worked with OIDC to protect it with patents. Our next step was to form a company and license our technology, which we are now working to develop and expand. This new grant is an important step in that expansion process.”

While sales are still a ways in the future, Tenenbaum’s vision for the company is to produce and sell specific sxRNAs for targeting different types of problematic cells (e.g., senescent cells, cancer cells), to clients who use and manufacture organoids such as researchers working on Alzheimer's disease or pharmaceutical companies that want to screen drugs using an organoid system.

“We will likely partner with a company that manufactures organoid kits,” said Tenenbaum. “This is an emerging area. Many people are working with organoids to study diseases and test therapeutics. Companies are now beginning to make and sell kits to help researchers produce and study organoids more efficiently.

“We could potentially sub-license our technology to a company that would bundle our sxRNAs into their kits, or to a pharmaceutical company that develops and tests new drugs.”


About the University at Albany:

The University at Albany is one of the most diverse public research institutions in the nation and a national leader in educational equity and social mobility. As a Carnegie-classified R1 institution, UAlbany and its faculty and students are creating critical new knowledge in fields such as artificial intelligence, atmospheric and environmental sciences, business, education, public health, social sciences, criminal justice, emergency preparedness, engineering, informatics, public administration and social welfare. Our courses are taught by an accomplished roster of faculty experts with student success at the center of everything we do. Through our parallel commitments to academic excellence, scientific discovery and service to community, UAlbany molds bright, curious and engaged leaders and launches great careers.