Flagship Pioneering Bets on tRNA for Disease Treatment

Flagship Pioneering Invests in Novel tRNA-Based Therapeutics with Alltrna

Flagship Pioneering, a prominent investor notably involved with Moderna, revealed on Tuesday a new venture added to its growing portfolio of companies exploring RNA technologies. Following considerable attention surrounding mRNA advancements, a new company, Alltrna, will concentrate on the creation of medicines utilizing Transfer RNA, or tRNA.

Understanding mRNA and tRNA

Many are now acquainted with the concept of messenger RNA (mRNA), the genetic material utilized in the Moderna and Pfizer COVID-19 vaccines. mRNA functions as a blueprint, instructing cells to construct specific amino acids and assemble them into proteins.

Consider tRNA as a uniquely shaped molecule responsible for the actual process of assembling the amino acids dictated by the mRNA blueprint. Transfer RNAs are integral to the final stages of cellular function, translating genetic code into functional proteins within the body.

Alltrna’s Therapeutic Vision

Alltrna operates under the premise that a single tRNA molecule could potentially offer treatment for “thousands of diseases,” according to Lovisa Afzelius, an origination partner at Flagship and co-founding CEO of Alltrna, in a statement to TechCrunch.

The company has been in a preparatory phase for the past three years, during which a team of 30 individuals has been developing a comprehensive “platform” dedicated to tRNA therapeutic development.

“This molecule is fundamentally critical,” Afzelius stated. “However, it has been largely ignored as a therapeutic approach until now. We’ve created a broad tRNA platform enabling us to fully investigate the potential of tRNA biology.”

The Rise of Alternative RNA Technologies

The success of Moderna and Pfizer’s COVID-19 vaccines has provided compelling evidence of mRNA technology’s capabilities. This year has also witnessed increased funding for other alternative RNA projects.

In May, Flagship introduced Laronde, a company with the ambition to develop 100 distinct endless RNA (eRNA) products and drug programs over the next decade. (eRNA is a unique RNA type developed by Flagship, designed to extend the therapeutic effects of medications or create sustained expression of therapeutic proteins).

Laronde subsequently secured approximately $440 million in Series B funding this year, with investments from Flagship, as well as funds managed by T. Rowe Price, CPP Investments, Fidelity Management and Research Company, Federated Hermes Kaufmann Funds, and BlackRock.

Growing Interest in tRNA-Based Medicine

While still a relatively nascent field, tRNA-based medicine is gaining increasing recognition. Three startups – ReCode Therapeutics, Shape Therapeutics, and Tevard Biosciences – have collectively raised $240 million to advance tRNA-based therapeutics, as reported by C&EN in September 2021.

Alltrna’s Potential for Broad Impact

Alltrna emphasizes tRNA’s potential to address a vast spectrum of diseases. Theonie Anastassiadis, a principal at Flagship and co-founder and chief innovation officer of Alltrna, highlights tRNA’s capacity to regulate “many aspects of translation.”

For example, specific “proliferation tRNAs” are involved in cell division, and research suggests that reducing the activity of certain tRNAs could potentially slow down cell proliferation in cancer.

TRNAs can also rectify errors in genetic code. Some genes contain mutations that act as premature “stop” signals (stop codons). These signals prematurely halt protein production, leading to complications. Premature stop codons play a significant role in genetic diseases and may contribute to 10% to one-third of all inherited genetic disorders or cancers.

Afzelius explains that engineered tRNAs could potentially bypass these stop signals, enabling the complete assembly of proteins.

“These stop codons are consistent across numerous diseases. The same amino acid is required in all these proteins. We can utilize the same tRNA medicine across a wide range of genetic diseases,” she explained.

Building the Foundation for tRNA Therapeutics

Alltrna’s initial focus is on enhancing the tools necessary for tRNA-based medicine development. Current methodologies for expressing, measuring, modifying, and synthesizing tRNAs are described as “extremely technically challenging” by Anastassiadis.

“Our first step was to develop these proprietary tools as part of the platform,” she stated.

Future Plans and Investment

The development of this tRNA therapeutic platform represents the extent of the company’s publicly disclosed plans. Currently, Alltrna has not announced any partnerships, nor are they revealing the specific diseases they are targeting.

Flagship has initially invested $50 million in Alltrna, matching the initial funding provided to Laronde earlier this year. Afzelius indicates that the company will seek external investment “when the time is appropriate.”

*This article has been updated to reflect that methodologies developed by Alltrna for studying tRNAs are proprietary.