Sachi Bioworks publishes on immunotherapy drug-development in Life Sciences in Space Research




Reversing radiation-induced immunosuppression using a new therapeutic modality


May 11, 2022

Immune suppression poses significant health challenges for millions of patients undergoing cancer chemotherapy and radiotherapy treatment, and astronauts and space tourists travelling to outer space due to radiation-induced immune dysfunction. While a limited number of recombinant protein therapies, such a Sargramostim, are approved for accelerating hematologic recovery, the pronounced role of granulocyte-macrophage colony-stimulating factor (GM-CSF or CSF2) as a proinflammatory cytokine poses additional challenges in creating immune dysfunction towards pathogenic autoimmune diseases.

Sachi demonstrated its proprietary NanoligomersTM technology to develop a range of immunotherapies and present their approach to high-throughput drug-discovery, target validation, and lead molecule identification. The Sachi Nanoligomer™ molecules are programmably designed using their state-of-the-art bioinformatics and an artificial intelligence (AI)-based ranking method and synthesized as a safe and effective peptide-molecule chassis, where a single NanoligomerTM modality combines 6-different design elements to up- or downregulate gene expression of target gene, resulting in elevated or diminished protein expression of intended target. This method additionally alters related gene network targets ultimately resulting in pathway modulation. This approach was used to perturb and identify the most effective upstream regulators and canonical pathways for therapeutic intervention to reverse immunosuppression, and also to safely boost host immune system as a pathogen-agnostic anti-infective countermeasure.

The lead Nanoligomers™ identified in a screen of human donor derived peripheral blood mononuclear cells (PBMCs) upregulated Erythropoietin (EPO) and GM-CSF, and showed reversal of radiation-induced cytokine changes. The lead NanoligomersTM while upregulating key proinflammatory cytokines, also boosted anti-inflammatory cytokines like IL-10, maintain the balance between T-helper cells, and shown even boost T-regulatory (Treg) cells, which points towards safe upregulation/boosting host immune defenses without causing autoimmune diseases or imbalance between different elements of innate immune system. It was further tested in vivo in a mouse radiation-model with low-dose (3 mg/kg) intraperitoneal administration and was shown to regulate gene expression of epo in lung tissue as well as counter immune suppression. These results point to the broader applicability to Sachi’s approach towards drug-discovery, and potential for further translation of our lead molecule as reversible gene therapy to treat adverse health outcomes in immunocompromised patients, or boost immune defenses as a broad-spectrum and pathogen-agnostic anti-infective (anti-viral, anti-bacterial, and anti-fungal).

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