Nanotechnology Orchestrated Viral Annihilation (NOVA) – DTRA

The Defense Threat Reduction Agency (DTRA), R\&D Chemical and Biological Technologies Directorate — Medical Division, in support of the Joint Science and Technology Office (JSTO) and in collaboration with CPE-CBRND, is seeking prototype **nanotechnology-based medical countermeasures** for viral threats to the warfighter in both pre- and post-exposure scenarios.
Today, countermeasures are typically developed one-to-one — a single countermeasure per virus, each tuned to a specific immune response or enzyme. That specialization slows responsiveness, lengthens lead times, and limits the Government’s ability to protect forces against multiple, emerging, or unknown viral threats at once. Nanotechnology offers a “bottom-up” alternative: broad-spectrum, biocompatible, biodegradable, multifunctional, and easily deployable countermeasures that can also mitigate the fallout of preexisting infection.
## Problem Statement
CPE-CBRND and JSTO support the warfighter through the development of medical countermeasures for biological and chemical threats, both known and unknown. A critical component of this development process is developing medical countermeasures with broad-spectrum activity.
Each medical countermeasure typically addresses only one viral threat. This specialization limits responsiveness, increases lead times, and constrains the Government’s ability to address multiple or emerging threats simultaneously.
There is a need to explore new technologies that can address multiple viral threats and simultaneously mitigate fallout caused by preexisting infection.
## Overall Objective
**LOE 1: Prototype and Demonstrate Broad-Spectrum Antiviral Nanotechnology Countermeasures**
**Narrative:** Develop and demonstrate a nanotechnology-based countermeasure prototype that neutralizes multiple viral threats through decoy and immunomodulatory mechanisms. This validates whether a single platform can replace the traditional one-virus, one-countermeasure model.
**Objectives:**
●        Develop a nanotechnology prototype functionalized through cellular membrane modifications.
●        Demonstrate in vitro activity against at least five (5) different viruses.
●        Demonstrate in vivo activity against at least one (1) virus in a relevant nonclinical model.
●        Validate the prototype’s ability to act as a cellular decoy to intercept viral threats.
●        Assess the prototype’s ability to act as a cytokine sponge to mitigate inflammatory fallout from preexisting infection.
●        Document efficacy and safety outcomes to inform go/no-go and future transition decisions.

**LOE 2: Prototype and Validate Ruggedized, Multi-Route Formulations**
**Narrative:** Adapt the prototype for field use by developing ruggedized formulations deliverable through multiple routes of administration. This tests whether the countermeasure can be stored, transported, and administered under austere operational conditions.
**Objectives:**
●        Design or adapt the prototype formulation for administration via multiple routes.
●        Develop ruggedized formulations, for example dried and heat-stable presentations.
●        Conduct stability testing under operationally relevant storage and transport conditions.
●        Evaluate whether ruggedized and alternate-route formulations retain antiviral activity against defined success criteria.
●        Gather qualitative and quantitative feedback from Government end users on deployability.
●        Document results and recommended formulation(s) to inform follow-on development.

**LOE 3: Demonstrate Scalable Manufacturing and Define a Regulatory Pathway to Licensure**
**Narrative:** Demonstrate that the prototype can be manufactured at scale and define a credible regulatory pathway toward licensure. This reduces transition risk by confirming the technology can move from nonclinical demonstration to the clinic.
**Objectives:**
●        Develop a scalable manufacturing process capable of supporting production through Phase 1 clinical trials.
●        Demonstrate manufacturing consistency, quality, and reproducibility across production lots.
●        Define a regulatory strategy and pathway to licensure, including anticipated FDA engagement.
●        Identify technical, manufacturing, and regulatory risks along with mitigation approaches.
●        Develop recommendations for follow-on clinical development, production, or refinement.
●        Ensure results are documented to support Government transition and acquisition decisions.