• while there are different definitions of concept of programmable therapeutics (you have programmable cells, synthetic bio, CRISPR) → programmable medicines can be defined as platform with modular components that can shorten the time from new target to drug candidate + have a higher level of personalization and precision (they don't necessarily have a specific function or target, but the processes in the drug can be programmed and altered, making it easier for a combination of therapies to ultimately be programmable)
• to identify drug target, new screens and tests are required to find chemical matter that binds to a target of interest (involves assays are developed to measure biological activity in vitro + animal models) → additionally, require new manufacturing process that is developed to require to mass produce the drug and its materials + requires toxicology and clincal trials
  • Companies that inspire this trend: Genetech, Deep Genomics, Laronde, Moderna and eRNA, Omega Therapeutics, CRISPR-gRNA etc. → most of these companies are based around RNA discoveries, which is fundamentally a glorified nanobot → in fact, the majority of biotech companeis are based on novel discoveries, yet none actively assist in the discovery of new technology (apart from Deep Genomics) and effectively provide a level of robustness
    • while a lot of these companies do offer a level of programmability, they aren't necessarily wide-scope as we think → i.e. what if we can code a new sequence in your DNA to produce a new class of riboswitches that create chemical signal when a specific bacteria is detected, and through a simple, non-invasive method like a patch, rewrite that sequence or add a new sequence based on the new bacteria given that there is a feedback loop
      • Programmable = specific but broad, personalized yet robust, minimally-invasive but interfaceability } refering to different parts of the programmable therapeutics pipeline
  • this directly ties back with the idea of not just optimizing, but ultimately bypassing the current model for approving drugs and therapies through clinical trials → government regulators start anew for each drug candidate, and clinical development beigns the arduous march therough safety and tolerability studies, dose selection, registrational trials, and regulatory approval
• the idea of modularity or programmability is under the assumption that the time decreases and probability of success from idea to medicine increases
• simplifying the choice of target for example can help us have deeper understanding of casual human bioogy → advances in genetics and pathophysiology are helping to de-risk many processes from drug candidate validation to delivery mechanisms with limited pre-clinical studies
• a critical part of the model is the delivery vector (lentiviral, AAV gene therapy, mRNA for encoding proteins) → what changes is just the payload of coding sequence, but we can add levels of sophistication on top of this (strucuture = functions)
  1. delivery vector that has been de-risked in terms of safety and has capacity to easily scale for manufacturing
  2. payload that can be packaged into delivery vector to create new drug product