Because of the mRNA-based Covid-19 vaccine, messenger RNA has become mainstream knowledge. Flagship Pioneering, the venture capital firm that established the mRNA company Moderna, has been working on a new start-up company to solve a neglected form of RNA. With the support of Flagship’s $50 million in cash, this new company called Alltrna is being launched, with the goal of adopting a new method to treat a range of diseases.
Messenger RNA serves as instructions for making proteins. Alltrna’s focus is on transfer RNA, or tRNA. These molecules play a key role in ensuring that the correct amino acids (the building blocks of proteins) are correctly added to the protein when it is made. Lovisa Afzelius, founding partner of Flagship and founding CEO of Alltrna, described this part as the last key part of the protein manufacturing process. This part ends with a sequence called a stop codon, which is a genetic instruction that marks the end of protein synthesis.
In some diseases, the protein manufacturing process stops prematurely due to premature stop codons. The result is a truncated protein that causes disease. Alltrna aims to design tRNAs that can recognize stop codons and provide amino acids needed to complete the protein manufacturing process. If it is effective, the treatment should restore the production of the appropriate length of protein.
Moderna may be the most famous company created by Flagship, but the company’s research is leading the development of other RNA companies.Last May, the company Launched Laronde, a biotech start-up company that develops circular RNA drugs with the potential to continuously create proteins. Alltrna was established in Flagship in 2018. Theonie Anastassiadis, Alltrna’s co-founder and chief innovation officer, said that during Flagship’s exploration of tRNA, she was surprised to find that the sequence of tRNA is very different. The chemical modification of these molecules confers additional functions. Anastassiadis said that it suddenly occurred to her that controlling these molecules could provide a way to develop new programmable drugs to repair mutations in the genetic code.
“If you can program drugs, you can control different but influential areas of biology,” Anastasiadis said.
Scientists have known tRNA for a long time. But Afzelius said that no one has considered how to use it as a treatment for disease. Alltrna’s tRNA research requires the creation of a new technology toolbox. Anastassiadis explained that the basic tools for asking simple biological questions were not built for tRNA biology. This startup uses machine learning technology to understand tRNA biology. With this understanding, the company designed new tRNA molecules and then tested them in laboratories and animals using proprietary detection methods to measure tRNA properties, such as their stability and activity.
Afzelius said that collecting and analyzing data on tRNA allows Alltrna to optimize the design of the molecule to achieve the desired therapeutic properties. She declined to give any details about these properties, such as how they will be delivered to the cells or how long tRNA therapy can last. Anastassiadis said that a unique feature of this method is that it retains the internal mechanism of cell self-regulation, and the cell continues to be able to respond to internal and external stimuli.
Premature stop codons have been identified as the cause of many diseases, including cystic fibrosis, Duchenne muscular dystrophy, β-thalassemia and several types of cancer. Afzelius said that Alltrna has not disclosed which diseases are its targets, only that the company is building its drug pipeline extensively, “projects across the entire range of tRNA biology.” But she added that if the stop codon changes in many proteins It is possible to solve all these problems with the method of Alltrna.
“We can use one tRNA drug to treat thousands of rare or common diseases,” she said.
Picture from Alltrna
