A self-amplifying RNA-based synthetic nanobody platform for next-generation therapeutics - Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. The rapid development and deployment of therapeutic agents are critical to our ability to counteract rapidly progressing diseases. In particular, recombinant antibodies are a major tool against pathogens that, in contrast to prophylactic agents, provide immediate protection against infection and disease. In addition, antibodies are a proven antigen-binding framework that underpin many therapeutic modalities (e.g., CAR-T cells) used to treat a wide range of diseases. However, most therapeutic antibodies are produced by animal immunization—a process that suffers from significant bottlenecks in feasibility, cost, turnaround time, and scalability; furthermore, because antibodies are typically administered in protein form, both their manufacture and delivery via intravenous administration create considerable logistical challenges that limit their ability to be deployed rapidly. Collectively, existing methods to produce and deliver antibodies are unsuitable to counteract a rapidly progressing disease and, more broadly, to make antibodies the go-to solution for cost-effective, rapid, on-demand therapeutics. Our aim is to develop and evaluate a programmable technology platform that will transform antibody-based therapeutics, thus establishing a foundation for next-generation protein countermeasures and therapeutics. We will accomplish this through the synergistic merger of two synthetic biology technologies developed by our team. The first is a yeast-based platform for rapid, highly-scalable nanobody discovery and evolution, which can be automated and deployed to produce potent, synthetic nanobodies against any known viral pathogen (or protein target) in a matter of weeks. The second is our modified-nucleotide-based durable transcript-based technology, which enables nanobody and other protein cargo to be encoded in self-sustaining transcript vectors that are long-acting and conveniently delivered. Bringing these production and delivery technologies together, we will establish a new platform for durable transcript-encoded antiviral nanobodies that is highly scalable, cost effective, and provides effective protection against any viral infection. As a proof-of-concept, we will use our platform to develop durable transcript-based nanobodies against the flavivirus genus, identified by the NIH as harboring significant pandemic potential. We will leverage the platform scalability to not only generate highly specific antivirals against major flaviviruses that can be rapidly deployed in the field, but also–in line with a NIH-supported concept in disease preparedness. The inherent programmability of the two underlying technologies will allow rapid development of countermeasures against any viral pathogens and unlock durable transcript-encoded therapeutics for a wide range of diseases, including the design of personalized cancer therapies
