Optimization of Therapeutic Protein PEGylation by Integrating Coarse-grain Simulation and Cell-free Protein Synthesis
About This Grant
ABSTRACT The development of protein-based therapeutics has ushered in a new era of precision medicine, delivering hope and healing to millions facing severe and life-threatening conditions. Unfortunately, as natural biopolymers, protein therapeutics have fundamental limitations compared to small molecule therapeutics. Specifically, most proteins found outside their native location in the body are degraded, recognized by the immune system, lose stability/function, or are naturally cleared—a fatal flaw for a therapeutic. To overcome these limitations, therapeutic proteins may be functionalized with chemical groups to obscure their identity or increase stability. In 1990, the FDA first approved the covalent attachment of the polymer polyethylene glycol (PEG) to therapeutic proteins towards this end. When done properly, PEGylation improves the pharmacokinetic half-life, provides some masking from the immune system, and reduces side effects due to lower dosage frequency. The problem is that PEG attachment can only be done with certain amino acids (e.g. lysine, N-terminus), so control is very limited. Additionally, covalently attaching a PEG molecule to a protein is complex because this chemical modification alters the interactions and positions of the amino acid side chains, disrupting protein function. This disruption commonly outweighs the benefit, such that only 3% of FDA approved therapeutic proteins are PEGylated. This work seeks to greatly expand the benefit of PEGylating protein therapeutics by combining state of the art, computationally efficient coarse-grain molecular simulations with rapid cell-free protein synthesis and site- specific functionalization. Preliminary results have demonstrated that this simulation approach can predict with significant accuracy the optimal amino acid among the hundreds in a protein to target for PEGylation. Additionally, the cell-free protein synthesis approach allows for site-specific incorporation of a uniquely functionalized unnatural amino acid at any desired position—a capability which enables site-specific optimization of PEGylation and is crucial to broad application of the method. Using a design-build-test-learn strategy, parameterization of PEG-amino acid interactions will be incorporated into the simulation for the first time, which is hypothesized to greatly increase its accuracy. This approach will be validated with two protein therapeutics which have not yet been optimally PEGylated (Onconase for Mesothelioma/Ebola Virus Disease treatment and Crisantaspase for Acute Lymphoblastic Leukemia treatment) to improve their efficacy by increasing their activity, stability and retention.
Grant Summary
Optimization of Therapeutic Protein PEGylation by Integrating Coarse-grain Simulation and Cell-free Protein Synthesis is a NIGMS - National Institute of General Medical Sciences grant providing up to $558K for university, nonprofit, healthcare org. Applications are due 2029-06-30 (open). Check eligibility and apply with FindGrants.
Not quite the right fit?
Search 9,000+ open grants, or get matches ranked for your organization — free.
Focus Areas
Eligibility
How to Apply
Up to $558K
2029-06-30
- 1Confirm your organization is eligible for Optimization of Therapeutic Protein PEGylation by Integrating Coarse-grain Simulation and Cell-free Protein Synthesis from NIGMS - National Institute of General Medical Sciences, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIGMS - National Institute of General Medical Sciences before the deadline.
Don't want to draft it yourself?
We'll draft the complete application against NIGMS - National Institute of General Medical Sciences's requirements, run a quality review, and email you a submission-ready PDF plus an editable Word doc within 5 business days. Most orders deliver in 24-48 hours. Flat $399, any grant size.
AI Requirement Analysis
Detailed requirements not yet analyzed
Have the NOFO? Paste it below for AI-powered requirement analysis.
Optimization of Therapeutic Protein PEGylation by Integrating Coarse-grain Simulation and Cell-free Protein Synthesis: Frequently Asked Questions
Who is eligible for the Optimization of Therapeutic Protein PEGylation by Integrating Coarse-grain Simulation and Cell-free Protein Synthesis?
Optimization of Therapeutic Protein PEGylation by Integrating Coarse-grain Simulation and Cell-free Protein Synthesis is offered by NIGMS - National Institute of General Medical Sciences and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Optimization of Therapeutic Protein PEGylation by Integrating Coarse-grain Simulation and Cell-free Protein Synthesis provide?
Optimization of Therapeutic Protein PEGylation by Integrating Coarse-grain Simulation and Cell-free Protein Synthesis provides up to $558K per award from NIGMS - National Institute of General Medical Sciences. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Optimization of Therapeutic Protein PEGylation by Integrating Coarse-grain Simulation and Cell-free Protein Synthesis deadline?
Applications for Optimization of Therapeutic Protein PEGylation by Integrating Coarse-grain Simulation and Cell-free Protein Synthesis are due 2029-06-30 (open). Because deadlines can change, verify the date with the funder, NIGMS - National Institute of General Medical Sciences, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Optimization of Therapeutic Protein PEGylation by Integrating Coarse-grain Simulation and Cell-free Protein Synthesis?
To apply for Optimization of Therapeutic Protein PEGylation by Integrating Coarse-grain Simulation and Cell-free Protein Synthesis, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIGMS - National Institute of General Medical Sciences.