【Core Technique Introduction】
 The hexa-lactoside delivery system for siRNA therapeutics and pharmacokinetic platform is related to one of the six major core strategic industries’ plan announced in current governmental policy. The siRNA, due to their specific inhibition of certain gene sequences, can target and inhibit diseases specifically, even leading to treatments. However, their challenge lies in their negatively charged backbone, which repels against the negatively charged cell membrane, necessitating targeting molecules to enhance tissue-specific delivery. Internationally, triantennary N-acetyl galactosamine is widely used as a liver-targeting molecule for siRNA delivery. However, its intracellular release efficiency from endosome escape is only 0.01%. The triantennary N-acetyl galactosamine can serve as a liver-targeting molecule for drug delivery primarily because the asialoglycoprotein receptor (ASGPR) on the surface of hepatocytes specifically binds to molecules with terminal galactose residues. The unique and innovative hexalactoside of NARI exhibits high specificity for the ASGPR in the liver and can thus serve as a targeting molecule for liver drug delivery systems. Preliminary evidence obtained suggests that hexalactoside indeed has the potential to effectively deliver siRNA to the liver and inhibits the production of specific protein. Additionally, NARI owns global technology patents and the award for siRNA radiolabeling, which can assist domestic research in siRNA pharmacokinetics in the future. By dosing less than 30 nmol of siRNA, it is possible to have continuity in vivo imaging, showcasing recognized professional capabilities. 



Figure 1.Protein “X” production inhibition level by the delivery systems of siRNA only, hexalactoside-siRNA (HL-siRNA) and tri-galactosamine-siRNA(TG-siRNA) into HepG2, respectively. The results showed HL-siRNA delivery system has better effect for protein inhibition in HepG2.


Figure 2.An illustrative diagram of hexalactoside function as an imaging agent by radiolabeled with radioisotopes or delivers cargo like siRNA for liver-targeted treatments.


Figure 3.The National Atomic Research Institute owned siRNA pharmacokinetic platform, which can assist pharmacokinetic study for siRNA by less than 30 nmol of siRNA and continuous in vivo imaging.

【Project planning/technological applications】
Currently, major pharmaceutical companies worldwide are prioritizing the development of siRNA therapeutics, creating effective and secure drug delivery systems and applying new patents. NARI has dedicated years in researching and developing hexa-lactoside imaging agent, acquiring key technologies and patents during the process. In 2024, NARI plans to introduce siRNA synthesis tool and establish core technology for synthesizing hexa-lactoside-siRNA complex.
 
【Future layout】
Hexa-lactoside demonstrates effective targeting to asialoglycoprotein receptors on the hepatocyte membrane. It can serve as a hepatic imaging agent when labeled with radioisotopes or as a carrier for delivering cargo such as siRNA for liver-targeted therapies. Leveraging hexa-lactoside synthesis techniques and patents, the objective is set to establish a hexa-lactoside siRNA delivery platform. This initiative will further advance the impact of hexa-lactoside on liver-targeted healthcare and foster the growth of the local precision medicine industry.

【Contact Information】
Name： Researcher Wang, Mei-Hui
Tel：886-3-4711400 extension 7162
E-mail：mhwang@nari.org.tw
 
Name： Assistant Researcher Yang, Chun-Hung
Tel：886-3-4711400 extension 7013
E-mail：ych2336@nari.org.tw