UAlbany Chemist Funded to Advance Search for RNA’s ‘True’ Sequence

A man wearing a plaid button-down shirt and khaki pants poses, smiling, next to a lab bench covered in various pieces of chemistry equipment including pipettes, latex gloves, and plastic bottles containing clear liquids.
Associate Professor Shenglong Zhang pictured in his RNA Institute lab at the College of Arts and Sciences. (Photo by Erin Frick)

By Erin Frick

ALBANY, N.Y. (Jan. 30, 2025)—University at Albany’s Shenglong Zhang, associate professor in the Department of Chemistry at the College of Arts and Sciences, is breaking new ground in understanding how RNA shapes health, with a focus on sequencing RNA modifications that give rise to disease. 

Zhang recently received $1.6 million from the National Human Genome Research Institute, a branch of the National Institutes of Health, to advance his lab’s pioneering technology for sequencing RNA and its modifications, in collaboration with partners at Columbia University and the University of Utah. 

This work is part of a growing global effort to uncover the true sequence of RNA, which includes not only the basic RNA sequence comprised of the nucleotide bases adenine (A), cytosine (C), guanine (G) and uracil (U), but also chemical modifications that occur on these bases, which can cause disease. 

By enabling precision profiling of RNA modifications, Zhang’s research will help facilitate transformative impacts in personalized medicine, disease treatment and the development of safer, more effective RNA therapeutics.

“Our lab has developed a method that uses mass spectrometry to sequence RNA modifications in transfer RNA (tRNA) with unprecedented granularity,” said Zhang, who is also part of UAlbany's RNA Institute. “On average, there are about a dozen different nucleotide modifications per tRNA molecule. This technology, called Next Generation Mass Spectrometry-based Sequencing, is the first of its kind to successfully read the complete sequence of tRNA, including its diverse nucleotide modifications simultaneously. By providing a comprehensive and unbiased analysis of RNA modifications, this method fills a critical gap in the study of RNA diversity and its role in disease.”

RNA modifications are known to be involved in over 100 human diseases, including various cancers, diabetes and neurodegenerative conditions like Alzheimer’s and Parkinson’s. However, understanding these modifications at a level helpful for biomedical applications has been limited by existing sequencing technologies. Conventional methods recognize RNA’s basic building blocks (A, C, G, U), but fail to account for their modifications, which bear important implications for disease diagnosis, treatment and RNA-based therapeutics. 

“Existing sequencing methods can only profile a small subset of modifications individually, typically one method per modification type,” Zhang said. “So far, of the 170 known RNA modifications, fewer than 12 types of modifications can be profiled. This funding will allow us to push the limits of our technology by enabling simultaneous sequencing of multiple RNA modifications, which will ultimately provide a more general tool for revealing true RNA sequences. This sort of advancement will prove valuable for anyone involved in RNA-based research.” 

Working with the UAlbany Innovation Center and the SUNY Research Foundation, Zhang’s company DirectSeq Biosciences is making strides to bring this technology to market. DirectSeq Biosciences collaborates with universities and other research institutions to analyze RNA samples from various sources, including tissues and body fluids. Moving forward, Zhang’s team aims to expand the platform’s user base to provide sequencing services for additional academic researchers, biopharmaceutical companies and regulatory bodies focused on RNA-based therapies.

“As we develop our sequencing technology further, part of our work will focus on sequencing tRNAs in various cellular and disease conditions, as well as sequencing additional types of RNA such as ribosomal RNA (rRNA),” Zhang said. “Our primary goal is to sequence multiple RNA modifications simultaneously across different RNA types, a critical step in scaling up our technology.”

The technology also holds promise for ensuring the safety and effectiveness of RNA-based drugs and therapeutics. The ability to detect non-target RNA sequences and quantify impurities is crucial for developing and improving RNA-based medicines and vaccines.