Rare Daily Staff

Flagship Pioneering has unveiled Alltrna, expanding its portfolio of RNA based bio platform companies with the first company focused on transfer RNA as a way to regulate the protein universe and resolve disease.

Founded at Flagship Labs in 2018, Alltrna has mapped tRNA biology to systematically design tRNA medicines and encode a unifying approach to treating both rare and common human diseases driven by shared genetic mutations. Flagship’s initial commitment to Alltrna is $50 million.

“Alltrna builds on the more than decade long exploration, conducted at Flagship Labs, focusing on the RNA world as a source of programmable therapeutic modalities,” said Noubar Afeyan, cofounder and chairman of Alltrna and CEO of Flagship Pioneering. “With Alltrna’s platform we are leveraging tRNAs as the critical gatekeepers of protein production to target our central translation code for unprecedented therapeutic effect.”

Several diseases, rare and common, stem from the same nonsense mutation, where the code for an amino acid has been mutated into a “stop” codon, according to Alltrna. This results in a truncated or shortened protein product that causes disease. Alltrna has designed a tRNA that can specifically read these stop codons and deliver the desired amino acid, thereby restoring the production of the full-length protein.

tRNAs not only play a central role in the translation of mRNA into proteins, but also are programmable molecules with a diverse biology of modifications and fragments that execute the complex code of multicellular life. Alltrna’s platform harnesses the combinatorial potential of the hundred-plus different modifications possible at each nucleotide position that are key to tRNA structure, function, and stability. The stable structure, small size, and vast diversity of tRNAs make them natural drugs, says the company. Alltrna uses all this information to design, modify, produce, and deliver tRNA molecules as new therapeutics.

“We have built the world’s first tRNA therapeutic platform by combining the extensive learnings at Flagship in RNA design and delivery with a reinforced learning framework that unlocks the relationship of tRNA modality to biological output, disease application, and drug design,” said Lovisa Afzelius, origination partner at Flagship Pioneering and founding CEO of Alltrna. “Since the company’s founding, we have established a deep understanding of tRNA biology and its diverse combinatorial modifications to systematically design, program, and deliver tRNAs to correct disease.”

Alltrna’s platform combines internal expertise and proprietary machine learning tools to unlock the entire tRNA biology space. The company will use its platform to advance a single tRNA medicine to restore disrupted protein production, regardless of target, for thousands of diseases with the same underlying genetic mutation. The company is looking beyond the role of tRNAs in properly adding amino acids into a final protein product to leverage how tRNA biology can provide an entire framework for the regulation and expression of the protein universe to treat disease.

“tRNAs are complex signaling molecules with their own syntax that provides them unprecedented adaptive mechanisms to control protein production, and ultimately, cell destiny,” said Theonie Anastassiadis, principal at Flagship Pioneering and cofounder and chief innovation officer of Alltrna. “At Alltrna, we have discovered how to speak the language of tRNA biology, providing a new therapeutic framework and flipping the current paradigm of target-driven drug development.”

Photo: Noubar Afeyan, cofounder and chairman of Alltrna and CEO of Flagship Pioneering

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