Almost a decade after identifying a new class of RNA, a group of scientists sparks interest from Takeda Ventures
Over the last several years, scientists have turned their attention to long noncoding RNAs (lncRNAs) — a mysterious class of naturally occurring molecules that don’t code for proteins, but fulfill important regulatory functions in the cell. Stefano Gustincich and his team identified a new class of them back in 2012, and now the scientists have pulled in seed funding to see if the molecules can go where current therapeutics can’t.
Gustincich, a professor at the Istituto Italiano di Tecnologia in Genoa, Italy, helped identify what he calls SINEUPs: a type of lncRNA that has the ability to specifically elevate protein translation. His lab published a paper on the molecules in Nature back in 2012, in which they said the data revealed “another layer of gene expression control at the post-transcriptional level.”
Since then, Gustincich has been in close collaboration with Piero Carninci and his team at the Riken Center for Integrative Medical Sciences in Yokohama, Japan. The scientists believe their discovery can lead to high-specificity therapeutics for any target in which mRNA is present, which eventually piqued the interest of Takeda Ventures partner Sarah Cole. On Wednesday, they unveiled a $12.8 million (£9.1 million) seed round to launch Transine Therapeutics.
“The SINEUP gives the ability to target a naturally expressed molecule in the cell, and in a very sensitive way boosts the expression of that particular target,” said Cole, who’s now VP of R&D.
SINEUPs have two main components, Cole said. First, you’ve got a binding domain that binds to mRNA. To increase expression, the molecule needs the activity of an embedded inverted SINEB2 sequence — hence the name.
“What’s particularly interesting about the SINEUP technology is the fact that it boosts protein translation in the cell,” she said. “But whereas other techniques and other therapeutic avenues such as protein replacement therapy or gene therapy may well lead the cell to overexpress a lot of your target protein, which can be problematic, SINEUPs are actually exerting a modest effect on protein translation.”
Cole says SINEUPs can essentially restore protein expression back to normal levels, getting at the “root cause” of genetic diseases caused by such deficiencies. Transine also believes SINEUPs could be used to modulate proteins that have regulatory effects. And because they’re small in size, SINEUPs can be delivered in a variety of different ways — including as naked oligonucleotides, or via viral vectors.
“If you’ve got a significant neurodegenerative disease, we would actually be able to also offer a therapy that could actually target a regulatory protein that could have a very strong impact on cell health,” Cole said.
To start, Transine is zeroing in on CNS diseases and ophthalmology. While Cole said she couldn’t share which specific indications the company will pursue first, the company’s other major investor offers a big hint: the Dementia Discovery Fund.
“Long non-coding RNAs are emerging as key cellular regulators which could be exploited as new therapeutic approaches for multiple indications,” Gustincich said in a statement. “Transine SINEUPs belong to this family and can be engineered to target almost any protein with exquisite specificity.”
The company is in the process of onboarding a CEO, who will formally join in July.