Advantages
- High Gene Expression Efficiency: This proprietary polylysine dendrimer derivative offers superior gene expression efficiency compared to conventional technologies.
- Low Toxicity and High Safety Design: This DDS carrier is composed of biodegradable materials, including polylysine dendrimer derivatives and anionic polymers, reducing accumulated toxicity. Additionally, the surface of the carrier is coated with an anionic polymer, further reducing toxicity and expected to provide high biological safety..
- Unique Nanoball Technology: Developed at Nagasaki University, this technology avoids dependence on patents related to other DDS technologies.
Technology Overview & Background
Nucleic acids, which are negatively charged polymers, have been widely utilized as tools for gene regulation and therapeutic agents. However, their effective delivery remains challenging due to electrostatic repulsion with the negatively charged cell membrane and their rapid degradation by enzymes in the body. To overcome these obstacles, various cationic polymers and lipids have been developed. Nonetheless, their use raises concerns regarding tissue toxicity caused by aggregation with blood components.
To overcome these limitations, researchers have developed an anionic DDS carrier, termed “nanoballs.” These nanoparticles are composed of nucleic acids, cationic polymers, and anionic polymers. Through careful material selection, nanoballs enable the efficient delivery of nucleic acids to target organs such as the lungs and spleen. Polyethyleneimine (PEI) has traditionally been used as the cationic polymer in nanoballs due to its effectiveness in gene expression. However, its non-degradable nature raises concerns about accumulation toxicity. While biodegradable cationic polymers address this issue, they often suffer from poor transferability from endosomes to the cytoplasm, resulting in suboptimal gene transfer efficiency.
 |
The research team focused on biodegradable polylysine dendrimers composed solely of lysine and sought derivatives with high gene transfer efficiency. In this study, they discovered that Phe-KG5, a polylysine dendrimer (KG5) modified at its termini with phenylalanine, exhibits minimal gene transfer effect on its own. However, when combined with other cationic compounds, it significantly enhances gene transfer efficiency. Additionally, they successfully developed an integrated dendrimer to optimize this effect. Furthermore, by incorporating Phe-KG5 into nanoball technology, they developed a formulation that achieves high gene expression efficiency while effectively minimizing toxicity.
Data Highlights
In Vitro Studies:
- Phe-KG5, a polylysine dendrimer (KG5) modified with phenylalanine, and Arg-KG5, a KG5 modified with arginine, were combined with plasmid DNA (pDNA) encoding luciferase and transfected into B16 cells. The resulting luciferase activity matched the performance of Lipofectamine 3000.
In Vivo Studies:
- As an integrated formulation, Arg-Phe-KG5, a KG5 derivative modified with both phenylalanine and arginine, was newly developed. Administration of c-Myc siRNA/Arg-Phe-KG5/γ-PGA to a mouse model of colon cancer peritoneal dissemination using Colon26 cells resulted in a significant tumor suppression effect. The nanoballs incorporating Arg-Phe-KG5 exhibited approximately 10 times greater effectiveness compared to those utilizing unmodified polylysine dendrimers.
Patent
Principal Investigators & Academic Institution
Assistant Professor Tomoaki Kurosaki (Nagasaki University Graduate School of Biomedical Sciences).
Expectations
TECH MANAGE CORP. is looking for a pharmaceutical company/start-up that is interested in development/evaluation of DDS carrier based on this research project. We also welcome companies interested in developing and evaluating gene transfer reagents based on this project. If interested, we would be delighted to arrange a meeting with our researchers to explore potential licensing/collaboration opportunities.
Project ID: TT-05082