- Alltrna's ML-driven platform computationally screened billions of tRNA molecules to precisely engineer therapeutic properties driven by tRNA sequences and chemical modifications.
- Alltrna presents data showing that ML-based algorithms can rapidly improve tRNA design and increase engineered tRNA activity through sequence and chemical modification optimization.
- In vivo data demonstrate that the platform can generate tRNAs that potently rescue protein production through readthrough of two of the most common premature stop codons in genetic diseases
cambridge, massachusetts, May 7, 2024 /PRNewswire/ — AltonaThe company, a pioneering company pioneering tRNA therapeutics to unlock transfer RNA (tRNA) biology and control the protein world to solve disease, today announced the American Society for Gene and Cell Therapy (ASGCT) At our 27th Annual Meeting, we announced the presentation of new data demonstrating the effectiveness of Alltrna. A machine learning (ML)-enabled platform optimizes the sequence and modification of natural tRNAs to achieve significant increases. in vivo Activity of reading premature termination codons (PTCs) caused by nonsense mutations.
“Alltrna’s ML-driven platform explores the vast combinatorial space of tRNA sequences and modifications at an unprecedented scale, potentially allowing us to generate more artificial tRNA oligonucleotides than there are atoms in the universe. ” states. Michelle C. Werner, CEO of Alltrna. “The data demonstrate the ability of his Alltrna platform to identify important combinations of tRNA sequences and modifications and precisely design significantly improved tRNA oligonucleotides. in vivo Activities. Using engineered tRNAs optimized for the two most common premature termination codons, we are advancing preclinical studies of our first stop codon disease indications. ”
tRNAs are programmable molecules with a diverse biology of sequence and modification that is key to structure, function, and stability. There is a possibility that there are about 10 people.34 Over 120 natural and synthetic modifications to the tRNA sequence and each nucleotide. Alltrna scientists applied high-throughput sequence optimization using ML-based screening to increase engineered tRNA activity approximately 100-fold. Optimization of the modification by ML further increased the engineered tRNA activity.
Data were presented on the optimization of engineered tRNA oligonucleotides to address two different PTCs (Arg-TGA and Gln-TAG).Both optimized tRNAs delivered using liver-targeted lipid nanoparticles (LNPs) showed robustness in vivo Activity in two transgenic mouse models. The first carries a human rare disease gene with a PTC mutation, and the second carries a reporter gene with a commonly different PTC. in vivo A model of stop codon disease. Previously presented Alltna in vitro Data on engineered tRNAs for Arg-TGA show that nonsense mutations can be read in 25 disease reporter models, 14 different genes, and 7 different mutation locations on a single gene, regardless of gene or location. Masu.
“These data were generated through the application of high-throughput sequencing and ML-driven modification optimization via Alltrna’s proprietary platform. in vivo “Activity of modified tRNA.'' Stephen W. Eichhorn, Ph.D., Head of Computational and Molecular Biology at Alltrna. “We also demonstrated that we can engineer strong tRNA activity against two different premature termination codons, each of which is highly prevalent in termination codon disease.”
About stop codon disease
Stop codon diseases include thousands of rare and common diseases caused by premature termination codons (PTCs), also known as nonsense mutations, where the code for an amino acid mutates into a premature “stop” codon. This produces truncated or truncated protein products that lack or have altered biological activity that causes disease. Approximately 10% of all people with genetic disorders have stop codon disease, which equates to approximately 30 million people worldwide. Alltrna is developing tRNA medicines that can read these PTC mutations and deliver the desired amino acids, thereby restoring full-length protein production.
About Altona
Alltrna unlocks tRNA biology to treat disease. The company's platform incorporates AI/ML tools to develop and deliver a diverse range of programmable molecules with broad therapeutic potential. Alltrna has an unprecedented opportunity to advance a single tRNA drug to decipher premature stop codons and unify the treatment of a wide range of diseases that share the same underlying genetic mutation. Alltrna was founded in 2018 by Flagship Pioneering. For more information, please visit: www.alltrna.com.
media contact
Jessica Yinglin,PhD, Little Dog Communications Co., Ltd., [email protected],+1.858.344.8091
Josephine SorboPhD, Flagship Pioneering, [email protected]
Source Altona
