WEST LAFAYETTE, Ind. \u2014 Published, peer-reviewed research shows a patent-pending, virus-mimicking platform technology developed at Purdue University improves upon traditional methods of targeting bladder cancer cells with messenger RNA (mRNA) therapies.<\/p>\n\n\n\n
The study, published in the Proceedings of the National Academy of Sciences<\/a>, highlights compelling features of the therapy-delivering system with respect to size, targetability, encapsulation efficiency, complex stability, gene expression and \u201cgreen\u201d manufacturability.<\/p>\n\n\n\n David Thompson<\/a> led the team conducting research about layer-by-layer elastin-like polypeptide nucleic acid nanoparticle (LENN). He is a professor in the James Tarpo Jr. and Margaret Tarpo Department of Chemistry<\/a> and a member of the Purdue Institute for Cancer Research<\/a> and the Purdue Institute for Drug Discovery<\/a>. Saloni Darji, a commercialization postdoctoral research associate, is the paper\u2019s lead author.<\/p>\n\n\n\n \u201cWe have validated that the LENN system can be freeze-dried and stored for several days as a powder and retain full biological activity after rehydration,\u201d Thompson said. \u201cWe also confirmed that this biomanufacturable system homes to the target tissue and neither alters the natural entry pathway to those tumors nor triggers an immune response. LENN traffics to the cancer cells then releases the mRNA within the cells, leading to expression of the protein encoded by the mRNA.<\/p>\n\n\n\n \u201cThese results could address challenges faced by lipid nanoparticle delivery systems, which must be continuously stored as liquids below minus 45 degrees Celsius to maintain their activity,\u201d he said. \u201cAdditionally, LENN system components are products of biological expression that enable a readily manufacturable delivery system.\u201d<\/p>\n\n\n\n Thompson disclosed LENN to the Purdue Innovates Office of Technology Commercialization<\/a>, which has applied for a patent to protect the intellectual property. Industry partners interested in developing or commercializing the system should contact Joe Kasper, assistant director of business development and licensing \u2014 life sciences, at jrkasper@prf.org<\/a> about track code 70252.<\/p>\n\n\n\n LENN particles mimic the multilayer structure of viruses to deliver nucleic acid-based therapies to targeted cells. It comprises two protective layers: an inner shell that condenses the therapies and an outer shell that protects it from degradation and evasion of the immune system.<\/p>\n\n\n\n To assess the stability of the freeze-dried formulations, Darji said concentrated formulations of LENN samples were diluted and initially frozen at minus 20 degrees C, followed by cooling to minus 80 C and lyophilization overnight. The lyophilized powders were stored at minus 20 C for three days.<\/p>\n\n\n\n \u201cSample rehydration was performed and formulations tested for structural integrity and encapsulation efficiency compared to fresh samples,\u201d she said. \u201cThese samples retained their functionality even after lyophilization, making them a promising mRNA vector system for therapeutic applications that require long-term storage.\u201d<\/p>\n\n\n\n Darji said the research into LENN\u2019s effects on entry pathways was conducted on bladder cancer cells because bladder cancer poses significant targeting and delivery challenges.<\/p>\n\n\n\n \u201cLENN can target the mRNA to a specific cell type based on that cell\u2019s surface information,\u201d she said. \u201cIn the case of bladder cancer cells, LENN targets a specific cell surface receptor already present on the tumor cell. The LENN system targets it and enters through the natural pathway.\u201d<\/p>\n\n\n\n Christina Ferreira, assistant research professor at Bindley Bioscience Center<\/a> with a courtesy appointment in Purdue\u2019s Department of Food Science<\/a>, conducted tests using multiple reaction monitoring (MRM) profiling, a Purdue-developed lipid analysis strategy.<\/p>\n\n\n\n Thompson said her work provided a different view of what happens once bladder cancer cells swallowed LENN particles.<\/p>\n\n\n\n \u201cMRM profiling showed that LENN doesn\u2019t alter the natural pathway of entry nor does it trigger any signs of an immune response, which would be a concern of long-term viability for this technology,\u201d he said. \u201cCurrent viral vectors trigger an immune response, which means redosing is ineffective because the immune system clears the dosing the second time. Christina\u2019s work gave insight that no immune reactions have been seen so far.\u201d<\/p>\n\n\n\n Thompson said the next phases of this project will focus on upscaling the system to support further preclinical evaluation.<\/p>\n\n\n\n \u201cThis includes efficacy and safety studies in the mouse model of bladder cancer in collaboration with Bennett Elzey<\/a> in the Department of Comparative Pathobiology<\/a> and the Purdue Institute for Cancer Research,\u201d he said.<\/p>\n\n\n\n This work is part of Purdue\u2019s One Health initiative<\/a>, which brings together research on human, animal and plant health.<\/p>\n\n\n\n The Purdue Innovates Office of Technology Commercialization<\/a> operates one of the most comprehensive technology transfer programs among leading research universities in the U.S. Services provided by this office support the economic development initiatives of Purdue University and benefit the university\u2019s academic activities through commercializing, licensing and protecting Purdue intellectual property. In fiscal year 2024, the office reported 145 deals finalized with 224 technologies signed, 466 invention disclosures received, and 290 U.S. and international patents received. The office is managed by the Purdue Research Foundation, a private, nonprofit foundation created to advance the mission of Purdue University. Contact otcip@prf.org<\/a> for more information.<\/p>\n\n\n\n Purdue University is a public research university leading with excellence at scale. Ranked among top 10 public universities in the United States, Purdue discovers, disseminates and deploys knowledge with a quality and at a scale second to none. More than 106,000 students study at Purdue across multiple campuses, locations and modalities, including more than 57,000 at our main campus in West Lafayette and Indianapolis. Committed to affordability and accessibility, Purdue\u2019s main campus has frozen tuition 14 years in a row. See how Purdue never stops in the persistent pursuit of the next giant leap \u2014 including its integrated, comprehensive Indianapolis urban expansion; the Mitch Daniels School of Business; Purdue Computes; and the One Health initiative \u2014 at https:\/\/www.purdue.edu\/president\/strategic-initiatives<\/a>.<\/p>\n\n\nLyophilization and entry pathways<\/h2>\n\n\n\n
All-Purdue collaboration<\/h2>\n\n\n\n
Next development steps<\/h2>\n\n\n\n
About Purdue Innovates Office of Technology Commercialization<\/h2>\n\n\n\n
About Purdue University<\/h2>\n\n\n\n