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Updated: May 5, 2026
08:29
Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
Published on: February 1, 2019
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Thioester-Containing Ionizable Lipids with Enhanced Endosomal Escape and Biodegradability for mRNA and tRNA Delivery
Álvaro Peña1, Esther Broset1, Enrique Lucia1
1Certest Pharma, Certest Biotec S. L., San Mateo de Gállego, 50840 Zaragoza, Spain.
Pharmaceutics
|May 4, 2026
Summary
New thioester-activated ionizable lipids (TAILs) enhance RNA therapeutic delivery by improving endosomal escape and biodegradability. This versatile platform shows potential for safe, next-generation RNA therapeutics.
Area of Science:
- Biotechnology
- Drug Delivery
- Organic Chemistry
Background:
- Lipid nanoparticles (LNPs) are advanced non-viral vectors for RNA therapeutics.
- Current LNPs require improved endosomal escape and biodegradability for transient nucleic acids like mRNA and tRNA.
Purpose of the Study:
- To design and synthesize novel, biodegradable ionizable lipids with thioester linkers.
- To identify lead candidates for enhanced RNA delivery vehicles.
Main Methods:
- Synthesized a library of ionizable lipids with thioester groups.
- Conducted in vivo structure-activity relationship studies.
- Evaluated LNP performance in mRNA expression and tRNA delivery models.
Main Results:
- Identified CP-LC-1272 as a lead candidate with enhanced endosomal escape and biodegradability due to acid-labile thioester bonds.
- LNPs with CP-LC-1272 maintained in vivo activity after 6 months of lyophilized storage.
- Demonstrated superior in vivo mRNA expression and comparable tRNA delivery efficiency versus SM-102.
Conclusions:
- Thioester-activated ionizable lipids (TAILs) offer rapid biodegradability, reducing accumulation risk.
- TAILs present a versatile and safe platform for next-generation RNA therapeutics, potentially enabling repeated or high-dose administration.
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