Version 1
: Received: 30 October 2024 / Approved: 31 October 2024 / Online: 31 October 2024 (13:31:52 CET)
How to cite:
Bravo Estupiñan, D. M.; Montaño-Samaniego, M.; Mora Rodríguez, R. A.; Ibáñez Hernández, M. A. Cationic Lipid Derived From a Basic Amino Acid: Design and Synthesis. Preprints2024, 2024102546. https://doi.org/10.20944/preprints202410.2546.v1
Bravo Estupiñan, D. M.; Montaño-Samaniego, M.; Mora Rodríguez, R. A.; Ibáñez Hernández, M. A. Cationic Lipid Derived From a Basic Amino Acid: Design and Synthesis. Preprints 2024, 2024102546. https://doi.org/10.20944/preprints202410.2546.v1
Bravo Estupiñan, D. M.; Montaño-Samaniego, M.; Mora Rodríguez, R. A.; Ibáñez Hernández, M. A. Cationic Lipid Derived From a Basic Amino Acid: Design and Synthesis. Preprints2024, 2024102546. https://doi.org/10.20944/preprints202410.2546.v1
APA Style
Bravo Estupiñan, D. M., Montaño-Samaniego, M., Mora Rodríguez, R. A., & Ibáñez Hernández, M. A. (2024). Cationic Lipid Derived From a Basic Amino Acid: Design and Synthesis. Preprints. https://doi.org/10.20944/preprints202410.2546.v1
Chicago/Turabian Style
Bravo Estupiñan, D. M., Rodrigo Antonio Mora Rodríguez and Miguel Angel Ibáñez Hernández. 2024 "Cationic Lipid Derived From a Basic Amino Acid: Design and Synthesis" Preprints. https://doi.org/10.20944/preprints202410.2546.v1
Abstract
One of the major challenges in gene therapy (GT) is the efficient and safe introduction of nucleic acids (NA) into eukaryotic cells. This process requires overcoming various biological barriers and navigating complex pathways to reach target cells and achieve their biological function. To address this obstacle, numerous transfection methods have been developed, including physical techniques and the use of genetic vectors, both viral and non-viral. However, until now, no transfection method is 100% safe and efficient. Within the spectrum of non-viral genetic vectors, cationic liposomes formed by cationic lipids (CL), stand out for their ability to protect and deliver therapeutic NA. These liposomes offer greater biocompatibility and lower immunogenicity compared to viral vectors, although they still do not match the efficiency of viral delivery systems. Consequently, ongoing research focuses on synthesizing a wide variety of cationic lipids in the search for compounds that provide high transfection efficiency with minimal cytotoxicity. This study aimed to design and synthesize a novel CL (CholCadLys) derived from natural cellular molecules for transferring genetic material to eukaryotic cells. The lipid was synthesized using: cholesteryl chloroformate for the hydrophobic region, cadaverine as a linker, and lysine for the polar region, connected by carbamate and amide bonds, respectively. Identification was confirmed through thin-layer chromatography, purification by preparative chromatography, and characterization via infrared spectroscopy and mass spectrometry. The synthesis yielded a 60% success rate, with stable nanoliposomes averaging 76 nm in diameter. Liposomes were formed using this CL and commercial neutral lipids, characterized by transmission electron microscopy and Nanoparticle Tracking Analysis. These liposomes, combined with plasmid DNA, formed lipoplexes used to transfect Hek-293 FT cells, achieving up to 40% transfection efficiency without cytotoxicity in the mixture of CholCadLys and CholCad. This novel CL demonstrates potential as an efficient, safe, and cost-effective gene transfer system, facilitating further development in gene therapy.
Biology and Life Sciences, Biology and Biotechnology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
