Issue link: https://www.e-digitaleditions.com/i/1534558
16 BioPharm International ® Next-Generation Biotherapeutics April 2025 www.biopharminternational.com Transfer RNA Page Header_ ketonuria, PKU. In the MMA model, we restored the protein that was missing by about 25%, and in the PKU mouse model, we restored the protein levels to 7%. That is a very encouraging protein restoration level because clinical experts have told us that with 1% or 2% protein restoration, you [can] ameliorate the clinical symptoms caused by loss of phenylala- nine hydroxylase in PKU that lead to elevated lev- els of specific toxins that actually need to stay low to avoid clinical complications. We are very happy with these data, and we are at this point progressing ver y nicely through our IND [investigational new drug] enabling program. We are very content with the progress that we are making to date. Assistance from AI/ML BioPharm: One of the biggest topics in the industry right now is artificial intelligence (AI). What roles are things like AI and machine learning (ML) play- ing as you attempt to move tRNA forward? Visser (Alltrna): We are absolutely using machine learning to design our tRNAs because of the wide range of design space of tRNA, which consists of somewhere between 70 to 80 nucleotides that can change in order. We also add specific chemical mod- ifications across the whole tRNA, so that makes the design space unmanageable with a human brain. We use machine learning techniques to design the tRNA and do the in-vitro testing, and then learn from t hat to come up wit h proposa ls for what to ma ke next. We have, over t he yea rs, lea rned to un lock this potential. For example, how do we improve on potency? We have learned how we can improve on activit y and all of the other elements that make a tRNA from an endogenous molecule to something that is actually a therapeutic. We also believe that A I/ ML is going to help us accelerate t he clin ica l development, in particular in boosting the field of model-informed drug development, the field that I've been trained in. So how do we leverage in vitro, in vivo, clinical data, real-world data, and can we learn from that and put that into mathematical models? AI/ML is going to help us with that, to make it more efficient to make those predictions going forward. So yes, we use AI/ML to design our tRNAs, but also it will help us in clinical development, and hope- fully, bring an important new therapeutic option to patients sooner. References 1. A l lt r na. A l lt r na | t R NA Med ici nes. Allt r na.com (accessed April 8, 2025). 2. Anastassiadis, T. and Köhrer, C. Ushering in the Era of tRNA Medicines. J. Biol. Chem. 2023, 299 (10) 105246. DOI: 10.1016/j.jbc.2023.105246 ■ DCAT Week 2025: Enzymatic RNA Synthesis Understanding the critical quality attributes of a whole cell is challenging, remarks Alison Moore, chief technical officer, Codexis, who spoke with BioPharm International® ahead of Drug, Chemical & Associated Technologies Association Week (DCAT Week) 2025 to find out the latest about the RNA therapy market and to get perspective on how enzymatic RNA synthesis is used to synthesize RNA molecules. "Manipulating RNA and just the beauty of having very specific transcriptional or translational control is really a lovely concept," Moore says. "Obviously, the public has seen the utility of mRNA in vaccine development, which remains revolutionary, We'll see where that goes in the future." Industry Outlook 2025: Cell Therapy Advancement Edwin Stone, CEO of Cellular Origins, sees two themes having the biggest impact to the bio/pharma industry: the expansion of glucagon-like peptide-1 (GLP-1) drugs and the growth of cell therapies from fourth- and third-line treatments to second-line treatments—but he also sees messenger RNA, the diversity of biologics, and new biological mechanisms as areas to pay attention to for the future of the industry. "I think the thing … we're perhaps just at the start of now, is being able to really broaden our ability to harness biology to go after diseases that we previously haven't been able to tackle. And of course, that's incredibly exciting," Stone says. Perspectives on the Future of RNA