Targeted delivery of mrna using endosomolytic peptide conjugates
Innovative mRNA delivery system using endosomolytic peptides for targeted and efficient cytosol entry and translation. Incorporates targeting ligands to enhance tissue specificity, leveraging natural nucleic acids and amino acids for reduced immunogenicity.
Overview
The proposed solution focuses on an innovative method for delivering mRNA into human cells using endosomolytic peptides. By conjugating mRNA with these peptides, the system enables efficient entry into the cytosol and subsequent translation. This approach also incorporates targeting elements, such as ligands or RNA aptamers, to ensure specificity for particular tissues or cell types, enhancing the potential for precision medicine applications.
Technical specifications
The technology involves constructing mRNA–peptide conjugates through a dual catalysis method that combines organocatalysis and enzymatic catalysis. This method allows for the attachment of targeting ligands, ensuring that the conjugates are directed accurately to designated targets. The components of the conjugate are entirely natural, consisting of nucleic acids and amino acids, which minimizes the risk of immunogenic responses. Additionally, mRNA is sourced from in vitro transcription, facilitating easier and faster manufacturability. Expertise in managing RNase 1 and other serum ribonucleases is integrated into the development process to enhance the stability and effectiveness of the mRNA delivery.
Technology readiness level
Currently at TRL 4, this technology has been validated in laboratory settings using cultured cells. Future validation will involve animal model testing, which will be conducted in collaboration with industry partners to further advance the development and application of this mRNA delivery system.
About Massachusetts Institute of Technology
MIT is a private research university known for intensive, interdisciplinary discovery and a global scale of sponsored research. Industry engages through a long-standing corporate partnership program, on-campus collaboration spaces, and shared-use facilities that enable rapid prototyping and characterization. The institute also operates a federally funded R&D center and maintains close adjacency to Kendall Square, allowing company teams to embed with faculty and students and accelerate translation. Research is supported by competitive federal funding from NSF, NIH, DOE, and the Department of Defense. A dedicated technology transfer office, standardized agreements, and an affiliated deep-tech accelerator support IP, licensing, and startup formation.
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