University of Toronto researchers developed chemically tuned transfer RNA that can bypass nonsense mutations, restoring full-length protein production in lab and preclinical models and enabling combination therapies for cystic fibrosis and other genetic disorders.
Engineered tRNA was designed to suppress nonsense mutations, restoring full-length protein production across lab and preclinical cystic fibrosis models.
In patient-derived organoids with multiple CFTR mutations, the tRNA plus the drug Trikafta produced a response when neither treatment worked alone.
Nonsense mutations account for about 11% of inherited genetic disorders, creating a shared target that could support a mutation-agnostic therapeutic strategy.
Researchers at the University of Toronto engineered transfer RNA (tRNA) molecules to ignore premature stop signals in mutated genes known as nonsense mutations. Those premature stops truncate proteins and can cause a wide range of inherited disorders. The team published their results in Science and tested the approach in laboratory and preclinical models focused on cystic fibrosis (CF).
Nonsense mutations insert a stop codon into the middle of a gene's coding sequence. The engineered tRNA is designed to read through those stop signals so cellular machinery can complete a full-length protein. To make the tRNA more effective, the team added a specific chemical modification modeled on natural tRNA marks. That modification increased the engineered tRNA's activity and longevity in cells.
The organoid experiment showed that the tRNA restored the missing portion of the CFTR protein, creating a target that the approved drug Trikafta could then modulate. That sequence — restore protein, then apply a modulator drug — produced a measurable response even when each intervention alone was ineffective.
Nonsense mutations are estimated to cause roughly 11% of inherited genetic disorders. Because the mutation type (a premature stop codon) is shared across many genes and conditions, a single engineered-tRNA strategy could potentially address multiple diseases without designing a unique gene therapy for each individual mutation.
Technical hurdles the team addressed
The team aims to refine delivery methods and advance preclinical development so the approach can move toward therapies that target nonsense mutations across different genes and tissues. The ultimate goal is a broadly applicable treatment strategy for subsets of cystic fibrosis, muscular and neurological diseases, and other conditions caused by premature stop codons.
The PROPEL program aims to control gene expression through RNA structure, building logic-gated RNA therapies that switch on only where and when intended, without altering the genome. The post RNAV8 Bio Joins ARPA-H Team to Pioneer Programmable RNA Medicines appeared first on GEN - Genetic Engineering and Biotechnology
Chemical engineers found a way to rapidly produce lipid nanoparticles of varying sizes, which could make it easier to develop new vaccines and therapeutics.
Our guest today is Dr. Nerissa Kreher, Chief Medical Officer of Alltrna. Nerissa brings two decades of rare disease drug development experience. The post Rewriting the rules of genetic medicine with tRNA therapeutics appeared first on Labiotech.eu . © Labiotech UG and Labiotech.eu. Unauthorized use and/or duplication o
A new genome-editing method, prime assembly, precisely inserts long DNA sequences into targeted genomic locations, potentially enabling mutation-agnostic gene therapies for diverse genetic diseases with fewer individualized edits. The post Prime Assembly Expands Genome Editing with Precise, Large-Scale DNA Integration
Randox Health The average person spends 20 years of their life in poor health. Let that sink in. But what if you could avoid that? While there are plenty of zeitgeisty ‘ solutions’ to better health floating around in the ether right now, many of them don’t come with a guarantee. It goes without saying that we’d go out
From readiness, longevity and AI insights to blood tests and movement assessments, we covered everything about the Health app’s redesign.
Loading more related stories...
Open the app view to save this story, compare related coverage, and continue from the same source.