Alltrna is a new biotech startup that is the first in the world to begin large-scale development of drugs based on transfer RNAs (tRNAs).
Behind the launch of Alltrna is the investment Flagship Pioneering of serial entrepreneur Noubar Afeyan, who has more than successfully invested in dozens of biopharmaceutical ventures. For example, Afeyan once believed in Moderna, whose ideas were viewed with skepticism by many, but which ended up producing a powerful mRNA vaccine against COVID-19. It brought unprecedented profits, making him a billionaire.
Alltrna, which began in 2018, has mapped tRNA biology in order to systematically design tRNA drugs and develop an entirely new approach to treating both rare and common diseases caused by shared genetic mutations. Flagship’s investment in Alltrna was $50 million.
Transfer RNA (tRNA) is a ribonucleic acid that enables the interaction of amino acid, the ribosome, and matrix RNA (mRNA) during translation. tRNA, without which proteins cannot be made, maps the genetic code to the desired amino acid and transfers it to the growing polypeptide chain, specifically attaching to the mRNA codon and providing the necessary conformation of the complex to form the new peptide bond.
Nevertheless, the importance of tRNA in the role of disease is completely overlooked. In addition to the proper arrangement of amino acids in the final protein product, tRNA is involved in the entire biological system of coordinating multicellular life. By controlling tRNA, it is possible to regulate proteins and eliminate the disease.
Alltrna’s expertise turns to machine learning to unlock the unique language of tRNA biology that is essential in creating programmable drugs. The desired properties of the latter are verified through automated and high-throughput in vitro assays followed by tests on animal models. The collected data are digitized and algorithmically processed with the generation of predictions regarding the optimal design of drug tRNA molecules with the desired activity, stability, selectivity, and delivery properties.
An example of the applicability of tRNA is a genetic mutation that results in a premature stop codon in the mRNA, reflected by the production of an incomplete truncated protein. Alltrna can design a tRNA that reads through this stop codon and then adds the correct amino acid to synthesize a normal protein. A number of pathologies are associated with the presence of premature stop codons, such as cystic fibrosis, Duchenne muscular dystrophy, spinal muscular atrophy, beta thalassemia, infantile neuronal ceroid lipofuscinosis, cystinosis, X-linked nephrogenic diabetes insipidus, Hurler syndrome, Usher syndrome, polycystic kidney disease, and cancer.
In addition to correcting faulty codes or mutations, another important area of interest for Alltrna is changing the ratio of tRNAs in cells to control which mRNAs are translated and which cellular programs are regulated.
Because tRNAs actually break down into smaller parts (fragments) characterized by different functions, it is possible to go beyond translation control, from affecting gene expression to retrovirus transcription.
Alltrna also claims to be able to develop a single tRNA drug, which, as a unified therapeutic backbone, is then programmed to the specifics of each particular disease to efficiently add the right amino acids needed for translation of a target protein.
Despite Alltrna’s statement about its primacy in the tRNA therapy sector, at least three other biotech companies are engaged in this field. Thus, ReCode Therapeutics is trying its hand at treating cystic fibrosis, Shape Therapeutics is working on Rett syndrome, and Tevard Biosciences has bet on the epilepsy of genetic nature, including Dravet syndrome.