Synthetic Technologies for Advancement of Research and Therapeutics (START)

Description:

NCATS Topics

This solicitation invites proposals in the following areas:

016 Synthetic Technologies for Advancement of Research and Therapeutics (START)

Fast-Track proposals will not be accepted.

Number of anticipated awards: 1-2

Budget (total costs, per award): Phase I: $225,000 for 9 months; Phase II: $1,500,000 for 2 years

PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED.

Phase II information is provided only for informational purposes to assist Phase I offerors with their long-term strategic planning.

Summary:

Traditional drug development pipelines are largely inefficient, with greater than 80% attrition of new drugs that move into Phase 2 clinical trials. Currently, it takes more than $1 billion and up to 14 years to bring a drug to market. One of the main contributors to this is our inefficiency to access unexplored biologically-relevant chemical space. About 40% of the chemical scaffolds found in natural products are absent in today’s medicinal chemistry repertoire. Natural compounds harbor chemical and structural diversity that can be utilized to develop novel treatments. Most importantly, natural compounds are evolutionarily optimized as drug-like molecules. Challenges of natural products in drug discovery and development include (i) extremely low yields and limited supply, (ii) complex structures that preclude practical synthesis, and (iii) complex structures posing enormous difficulty for structural modifications. Synthetic biology is making promising strides in reshaping and streamlining drug discover thanks to the recent advances in gene editing, gene synthesis, metabolomics and analysis techniques.

Topic Goals:

Current developments in synthetic biology have offered tools to design or modify organisms that can be used for a specific function, allowing for natural biological systems to be tailored as machines that produce desired compounds. Further, synthetic biology has a broad application and can be used to synthesize biologically relevant compounds and therapeutics that are not easily and/or not cost-effectively produced in a traditional laboratory setting. There is also an immense capability to scale-up production of said compounds using bioreactors and other platforms specific for growing microorganisms. Synthetic biology has the potential to accelerate the field of drug development by introducing tools and resources that can readily and efficiently produce desired compounds that are more cost effective.

The primary goal of this topic is to apply synthetic biology to produce and fully characterize both known and novel analogs of naturally occurring compounds to increase the diversity of compounds in drug libraries.

 

We are primarily interested in proposals focused on discovery, isolation and characterization of non-addictive natural compounds to treat pain, opioid abuse disorders and overdose. Other critical areas for therapeutic drug development will be considered pending strong scientific justification.

Phase I Activities and Expected Deliverables:

Phase I proposals must specify clear, appropriate, measurable goals (milestones) to be achieved. Phase I activities and deliverables may include the following:

• Formulate naturally occurring and biologically relevant pathways into a set of design rules that can then be used to engineer new candidate therapeutic molecules:

o Develop novel tools and technologies that would allow engineering of pathways into a host organism

o Develop genetic switches to control of gene expression

o Develop synthetic control systems for the production of bioactive molecules with therapeutic potential

Expand the current catalog of naturally occurring compounds and their analogs to enhance the diversity of chemical libraries:

o Identify and create biosynthetic gene clusters or pathways for the biosynthesis of natural products

o Apply synthetic biology tools to improve production of natural products from their native sources

o Utilize synthetic biology tools to assemble biosynthetic machinery and optimize yield for natural product production in heterologous hosts

o Synthesize, isolate and fully characterize novel bioactive compounds and demonstrate bioactivity of compounds following isolation

• Provide NCATS with all data and resources (i.e.: molecules created, producer organisms, etc.) resulting from Phase II Activities and Deliverables for independent validation of yield and bioactivity.

 

Phase II Activities and Expected Deliverables:

If Phase I objectives are met, feasibility is demonstrated, and there is sufficient evidence of commercial viability, the offeror can apply for Phase II. Phase II activities and deliverables may include the following:

• Continue the development of tools and technologies and prepare them for dissemination to the scientific community through, for example, licensing or servicing

• Develop a robust manufacturing process to scale-up production of novel compounds o Demonstrate bioactivity of compounds following scaled-up isolation

 

• Develop platforms that would allow large-scale applications of the developed tools and technologies as relevant to synthesis, isolation, characterization and modification of natural compounds

• Provide NCATS with all data and resources (i.e.: molecules created, producer organisms, etc.) resulting from Phase II Activities and Deliverables for independent validation of yield and bioactivity.

• In the first year of the Phase II contract, provide the program and contract officers with a letter(s) of commercial interest.

• In the second year of the Phase II contract, provide the program and contract officers with a letter(s) of commercial commitment.

• Present Phase II findings and final deliverables to NCATS Programs Staff via webinar.

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