Reversing radiation-induced immunosuppression using a new therapeutic modality

Area of Science:

• Biotechnology
• Immunology
• Drug Discovery

Background:

• Radiation exposure causes immune suppression, impacting cancer patients and space travelers.
• Current therapies like Sargramostim have limitations, and GM-CSF can exacerbate autoimmune issues.
• Targeting immune dysfunction requires novel therapeutic strategies.

Purpose of the Study:

• To develop a high-throughput drug discovery method for reversing radiation-induced immunosuppression.
• To identify effective upstream regulators and pathways for therapeutic intervention.
• To validate a lead Nanoligomer™ molecule for potential gene therapy applications.

Main Methods:

• Utilized a bioinformatics and AI-driven approach to design Nanoligomer™ molecules for gene expression modulation.
• Screened Nanoligomers™ in human peripheral blood mononuclear cells (PBMCs) to identify candidates reversing radiation-induced cytokine changes.
• Tested the lead Nanoligomer™ in a mouse radiation model to assess in vivo efficacy and gene regulation.

Main Results:

• The lead Nanoligomer™ upregulated Erythropoietin (EPO) and demonstrated significant reversal of radiation-induced cytokine alterations in human PBMCs.
• In vivo studies in mice showed the Nanoligomer™ regulated EPO gene expression in lung tissue and counteracted immune suppression.
• The Nanoligomer™ approach successfully modulated related gene networks and pathways.

Conclusions:

• The Nanoligomer™ platform offers a versatile approach for high-throughput drug discovery and target validation.
• The lead Nanoligomer™ shows potential as a reversible gene therapy to mitigate adverse health outcomes from radiation exposure.
• Further investigation into this nucleic acid-based therapy is warranted for clinical applications.