“Precise understanding of the delivery system necessary to develop mRNA, therapeutic DNA”


It is necessary to understand precisely the mechanism of the body to deliver substances of microribonucleic acid or deoxyribonucleic acid targeting genetic diseases.

Professor Lee Hyuk-jin of the Graduate School of Pharmaceutical Sciences at Ewha Womans University on Wednesday presented the development of RNA-based therapies and formulation of lipid nanoparticles (LNP) for in vivo administration during a online session organized by the Institute of Basic Sciences and Seoul National University.

Professor Lee Hyuk-jin from the Faculty of Pharmaceutical Sciences at Ewha Womans University explained the development of RNA therapy and formulation of lipid nanoparticles (LNP) for in vivo administration at a symposium Online on RNA Biology and Therapeutics organized by the Institute for Basic Science. and Seoul National University on Wednesday.

An mRNA needs protection to prevent it from decaying. Therefore, it must be transported and released from the endosome when it reaches the cell. When lipid nanoparticles (LNP) containing mRNA reach the cell, they undergo ionization and enter the cell.

“Speaking of mRNA, it has many advantages in target protein expression over conventional plasmid DNA,” Lee said.

For example, transfection of DNA and mRNA show very different intracellular trafficking pathways because DNA must enter the nucleus for transcription, while mRNA begins to express itself when delivered to the nucleus. cytoplasm, he explained.

LNPs are multicomponent lipid systems containing an ionizable lipid, a phospholipid, cholesterol, and a PEG-lipid. LNP systems are currently considered the most clinically advanced non-viral gene delivery system, safely and efficiently delivering nucleic acids.

While maintaining a stable endosomal structure until delivery, it is structured so that mRNA escapes the structure and is inserted by the process of ionization upon penetration between plasma membranes, Lee said.

“There is also a method for assigning characteristics to the surface of a single cell that targets a specific organ, either by introducing a ligand or by differently altering the profile of a protein adsorbed to the cell surface,” Lee said. “When selecting a ligand, it is necessary to first check whether the candidate substance could be ionized or not.”

However, he pointed out that mRNA still has limitations to stay at a locally delivered level. Since mRNA itself is easily degraded in the body, devices such as modified RNAs, vectors, and conjugates are needed.

Much less attention was paid to LNP before when researchers began to develop gene therapies.

“Synthetic mRNA is a very good system for rapid expression of target proteins, and delivery of this mRNA using lipid nanoparticles is a good medium for in vivo expression of mRNA,” said Lee. “It has the potential to be applied to various drugs to replace therapeutic proteins and used as mRNA vaccines.”


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