In long space exploration missions, astronauts are subjected to increased amounts of radiation exposure, which can lead to Acute Radiation Syndrome (ARS). While specific haemopoietic protein variants have been used as medical countermeasures (MCM) for ARS, several recent studies have identified need for inclusion of other targets to provide more effective radiation-exposure treatment. Recent multi-omics studies and radiobiological insights have also provided new gene targets to act as radiation MCM. Using a range of different proteins poses significant challenges and associated logistical challenges in their safe transportation and storage during space travel. Existing genetic manipulation methods are laborious, expensive, and inefficient. We propose to address this market and technology void by rapid design, build, and test of molecules using a proprietary FAST platform to target any gene in any organism. Our platform generates FASTmers (nucleic acid-nanoparticle-based high-throughput synthesis, purification, and delivery) to up- or down- regulate any desired gene. In our preliminary work, we have designed, built, and tested FASTmers in an accelerated fashion for several radiation markers. Eg., GM-CSF FASTmer demonstrated large-scale immunomodulation and specific haemopoietic protein regulation in human PBMCs during acute radiation exposure (3Gy). During this proposal, we will use individual FASTmers targeting specific genes related to ARS, and evaluate their efficacy using specific haemopoietic proteins and cytokine markers. Based on their efficacy, the top-ranked candidates will be evaluated as a combination therapy. Using detailed fractional factorial design and ensuing statistical analysis, we will identify the: 1) top therapeutic targets for ARS, both in monotherapy and combinations; and 2) ranked FASTmers as therapeutic assets for mono- and combination therapy, to further test and validate in animal and clinical testing (Phase II SBIR).
Our proposed work will result in rapid development of radiation countermeasures (single targets for first-in-class, and combination targets for best-in-class) for deployment in deep-space missions. These will be developed using our proprietary FAST platform for high-throughput, rapid, and targeted gene manipulation (reversible) of immune and other hematopoietic proteins, to utilize our own body to create these protective enzymes to counter and repair the damage caused by deep space radiation.
Due to desirable attributes such as cloning-free, simple, high-throughput, low-cost, and rapid deployment, Sachi’s FAST technology is preferred by biopharma and drug-discovery companies. We conservatively estimate that we can serve 5-10 drug-discovery contracts/therapeutic lead targets and assets during the first year of formal launch (2021).