Advantages
- KK-(EK)4-lipid functionalize various DDS carriers such as liposomes, extracellular vesicles (EVs), and lipid nanoparticles (LNPs)
- KK-(EK)4-lipid modified DDS carrier can be easily prepared using the post insertion method.
- Locally higher expression and systemically less expression due to enhancement of the cellular uptake at the site of administration of KK-(EK)4-lipid-modified mRNA/LNPs, which has potential application for genome-editing medicine
- KK-(EK)4-lipid-modified mRNA/LNPs are expressed tens to hundreds of times more efficiently in various cells and are not inserted into the genome, which has potential application for the creation of cellular medicine modified with various functional molecules.
Technology Overview & Background
Lipid based nanoparticles, such as liposomes, LNPs and exosomes are used as carriers for drug delivery. In recent years, the functionalization of DDS carriers has been reported to improve targeting and intracellular translocation for efficient delivery of therapeutic drugs.
Octaarginine (R8) peptide is a well-known cell-penetrating peptide(CPP). R8 peptide mediate the efficient cellular uptake of DDS carriers. However, unintended interactions between cationic CPPs and anionic materials, such as nucleic acids and exosomes, are often difficult to prepare. In addition, excess cationic material on the nanoparticles would cause cellular cytotoxicity and platelet aggregation.
Researcher focused on the high functionality and quality (HFQ) lipids. HFQ lipids were designed and synthesized to meet unique requirements regarding lipid components, dispersibility in water, and/or solubility in ethanol for preparing highly reproducible functionalized nanoparticles using microfluidic devices for the large scale preparation. In this study, researchers newly designed KK-(EK)4 lipids having a near neutral charge and enhance the intracellular translocation. KK-(EK)4-lipids is a simple functional molecule consisting only of lysine, glutamic acid and lipid, dispersible in water and soluble in ethanol.
This designed HFQ lipids include the EK repeat peptide motif. EK repeat peptide composed of negatively charged glutamic acid (E) and positively charged lysine (K). It has been reported that EK repeat peptides have anti-fouling effects and prolong the blood circulation times of nanoparticles and expected as substitute for PEG.
Publications & Patents
- Publication：Yuri Sugimoto, et al,, DrugDelivery, 30:1, 2191891
- Patent：PCT/JP2022/04354.
Principal Investigator & Academic Institution
Professor Shigeru Kawakami (Graduate School of Biomedical Sciences, Nagasaki University)
Development Stages & Plans
- Current stage：
Intramuscular administration of LNP with KK-(EK)4-lipid to mice demonstrated a higher luciferase expression in muscle and decrease in the liver than unmodified LNP.Researchers have confirmed significant in vitro mRNA expression of LNP with KK-(EK)4-lipid in lung cancer cell lines, dendritic cell lines, and muscle cell lines. They are currently planning in vitro expression in immune cells for the creation of cellular medicines for cancer.
- Next Step：
We can set up a meeting with the PI to discuss collaboration or R&D.
Expectations
TECH MANAGE CORP. is looking for a pharmaceutical company/start-up that is interested in licensing this invention for commercialization on behalf of Nagasaki University. We can also arrange a meeting with the PI of this invention. Please feel free to contact us with any requests you may have.
Project No. TT-04314