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Related Concept Videos

Nucleic acids02:43

Nucleic acids

Nucleic acids are the most important macromolecules for the continuity of life. They carry the cell's genetic blueprint and carry instructions for its functioning.
DNA and RNA
The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is the genetic material in all living organisms, ranging from single-celled bacteria to multicellular mammals. It is in the nucleus of eukaryotes and in the organelles, chloroplasts, and mitochondria. In prokaryotes, the...
Types of RNA01:23

Types of RNA

Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Nucleic Acids02:43

Nucleic Acids

Nucleic acids are the most important macromolecules for the continuity of life. They carry the cell's genetic blueprint and carry instructions for its functioning.
DNA and RNA
The two main types of nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA is the genetic material in all living organisms, ranging from single-celled bacteria to multicellular mammals. It is in the nucleus of eukaryotes and in the organelles, chloroplasts, and mitochondria. In prokaryotes, the...
Transfer RNA Synthesis02:36

Transfer RNA Synthesis

One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
Types of RNA01:20

Types of RNA

Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in regulating gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA Performs Diverse...
Nucleic Acid Structure01:25

Nucleic Acid Structure

The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms  a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA has a double-helix structure. The...

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Related Experiment Video

Updated: May 12, 2026

Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
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Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA

Published on: February 1, 2019

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Rational Design of Unsaturated, Thioether Ionizable Lipids for Enhanced In Vivo mRNA Delivery.

Eleni Samaridou1, Johanna Simon1, Moritz Beck-Broichsitter1

  • 1Merck KGaA, Frankfurter Str. 250, 64293, Darmstadt, Germany.

Advanced Healthcare Materials
|May 5, 2025
PubMed
Summary

Researchers optimized ionizable lipids for lipid nanoparticles (LNP) to improve messenger RNA (mRNA) delivery. New LNPs show a 200-fold increase in in vivo mRNA delivery, matching approved platforms

Keywords:
fusogenicityionizable lipidmRNA deliverypKarational lipid designstructure‐activity‐relationshipthe phospholipid

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Testing the In Vitro and In Vivo Efficiency of mRNA-Lipid Nanoparticles Formulated by Microfluidic Mixing

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Area of Science:

  • Biotechnology
  • Drug Delivery Systems
  • Molecular Medicine

Background:

  • Lipid nanoparticles (LNPs) are advanced delivery vehicles for mRNA therapeutics.
  • Understanding ionizable lipid structure-function relationships is key for efficient mRNA delivery.
  • Current ionizable lipids show limitations in in vivo performance.

Purpose of the Study:

  • To rationally design and structurally optimize ionizable lipids for enhanced in vivo mRNA delivery.
  • To investigate the impact of lipid tail and headgroup modifications on LNP performance.
  • To improve the efficacy and safety of mRNA-LNP therapeutics.

Main Methods:

  • Iterative optimization of ionizable lipid structure, focusing on lipid tails and headgroups.
  • In vitro assessment of protein expression and hemolysis.
  • In vivo evaluation of mRNA delivery efficiency and biodistribution.
  • Comparison with a market-approved LNP benchmark.

Main Results:

  • Engineered lipids with unsaturated tails and hydrophobic headgroups significantly improved in vitro protein expression.
  • Achieved over 200-fold improvement in in vivo mRNA delivery compared to initial designs.
  • Demonstrated reduced risk of hemolysis, enhancing safety profile.
  • New LNPs exhibited comparable in vivo delivery efficiency and biodistribution (liver, spleen) to a market-approved LNP.

Conclusions:

  • Rational design of ionizable lipids is crucial for overcoming in vivo mRNA delivery challenges.
  • Optimized lipids enhance LNP fusogenicity and pKa, leading to superior delivery.
  • Developed ionizable lipids/LNPs offer a promising platform for next-generation mRNA therapies and vaccines with improved efficacy and safety.