Optimization of phospholipid chemistry for improved lipid nanoparticle (LNP) delivery of messenger RNA (mRNA)

2021 ◽  
Author(s):  
Ester Alvarez Benedicto ◽  
Lukas Farbiak ◽  
Martha Marquez Ramirez ◽  
Xu Wang ◽  
Lindsay Johnson ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Messenger Rna ◽  
Lipid Nanoparticles ◽  
Nucleic Acid Delivery ◽  
Lipid Nanoparticle

Lipid nanoparticles (LNPs) have been established as an essential platform for nucleic acid delivery. Efforts have led to the development of vaccines that protect against SARS-CoV-2 infection using LNPs to...

Lipid Nanoparticles for Broad‐Spectrum Nucleic Acid Delivery

2021 ◽  
pp. 2101391
Author(s):  
Zuzana Hejdankova ◽  
Vaclav Vanek ◽  
Frantisek Sedlak ◽  
Jan Prochazka ◽  
Audrey Diederichs ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Broad Spectrum ◽  
Lipid Nanoparticles ◽  
Nucleic Acid Delivery

scholarly journals Role of Lipid-Based and Polymer-Based Non-Viral Vectors in Nucleic Acid Delivery for Next-Generation Gene Therapy

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2866 ◽  
Author(s):  
Aniket Wahane ◽  
Akaash Waghmode ◽  
Alexander Kapphahn ◽  
Karishma Dhuri ◽  
Anisha Gupta ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Nucleic Acid ◽  
Messenger Rna ◽  
Viral Vectors ◽  
Cationic Lipids ◽  
Nucleic Acid Delivery ◽  
Nucleic Acid Analogs ◽  
Organ Specific ◽  
Interfering Rna

The field of gene therapy has experienced an insurgence of attention for its widespread ability to regulate gene expression by targeting genomic DNA, messenger RNA, microRNA, and short-interfering RNA for treating malignant and non-malignant disorders. Numerous nucleic acid analogs have been developed to target coding or non-coding sequences of the human genome for gene regulation. However, broader clinical applications of nucleic acid analogs have been limited due to their poor cell or organ-specific delivery. To resolve these issues, non-viral vectors based on nanoparticles, liposomes, and polyplexes have been developed to date. This review is centered on non-viral vectors mainly comprising of cationic lipids and polymers for nucleic acid-based delivery for numerous gene therapy-based applications.

scholarly journals Tuning the Immunostimulation Properties of Cationic Lipid Nanocarriers for Nucleic Acid Delivery

2021 ◽  
Vol 12 ◽  
Author(s):  
Arindam K. Dey ◽  
Adrien Nougarède ◽  
Flora Clément ◽  
Carole Fournier ◽  
Evelyne Jouvin-Marche ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Messenger Rna ◽  
Cationic Lipid ◽  
Lipid Nanoparticles ◽  
Cationic Lipids ◽  
Fine Tuning ◽  
Target Cells ◽  
Substantial Impact ◽  
Lipid Nanocarriers ◽  
The Impact

Nonviral systems, such as lipid nanoparticles, have emerged as reliable methods to enable nucleic acid intracellular delivery. The use of cationic lipids in various formulations of lipid nanoparticles enables the formation of complexes with nucleic acid cargo and facilitates their uptake by target cells. However, due to their small size and highly charged nature, these nanocarrier systems can interact in vivo with antigen-presenting cells (APCs), such as dendritic cells (DCs) and macrophages. As this might prove to be a safety concern for developing therapies based on lipid nanocarriers, we sought to understand how they could affect the physiology of APCs. In the present study, we investigate the cellular and metabolic response of primary macrophages or DCs exposed to the neutral or cationic variant of the same lipid nanoparticle formulation. We demonstrate that macrophages are the cells affected most significantly and that the cationic nanocarrier has a substantial impact on their physiology, depending on the positive surface charge. Our study provides a first model explaining the impact of charged lipid materials on immune cells and demonstrates that the primary adverse effects observed can be prevented by fine-tuning the load of nucleic acid cargo. Finally, we bring rationale to calibrate the nucleic acid load of cationic lipid nanocarriers depending on whether immunostimulation is desirable with the intended therapeutic application, for instance, gene delivery or messenger RNA vaccines.

scholarly journals Tuning the immunostimulation properties of cationic lipid nanocarriers for nucleic acid delivery

2021 ◽  
Author(s):  
Arindam K Dey ◽  
Adrien Nougarede ◽  
Flora Clement ◽  
Carole Fournier ◽  
Evelyne Jouvin-Marche ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Messenger Rna ◽  
Cationic Lipid ◽  
Lipid Nanoparticles ◽  
Cationic Lipids ◽  
Fine Tuning ◽  
Target Cells ◽  
Substantial Impact ◽  
Lipid Nanocarriers ◽  
The Impact

Nonviral systems, such as lipid nanoparticles, have emerged as reliable methods to enable nucleic acid intracellular delivery. The use of cationic lipids in various formulations of lipid nanoparticles enables the formation of complexes with nucleic acid cargo and facilitates their uptake by target cells. However, due to their small size and highly charged nature, these nanocarrier systems can interact in vivo with antigen-presenting cells (APCs), such as dendritic cells (DCs) and macrophages. As this might prove to be a safety concern for developing therapies based on lipid nanocarriers, we sought to understand how they could affect the physiology of APCs. In the present study, we investigate the cellular and metabolic response of primary macrophages or DCs exposed to the neutral or cationic variant of the same lipid nanoparticle formulation. We demonstrate that macrophages are the cells affected most significantly and that the cationic nanocarrier has a substantial impact on their physiology, depending on the positive surface charge. Our study provides a first model explaining the impact of charged lipid materials on immune cells and demonstrates that the primary adverse effects observed can be prevented by fine-tuning the load of nucleic acid cargo. Finally, we bring rationale to calibrate the nucleic acid load of cationic lipid nanocarriers depending on whether immunostimulation is desirable with the intended therapeutic application, for instance, gene delivery or messenger RNA vaccines.

Mechanical stretching of cells and lipid nanoparticles for nucleic acid delivery

2021 ◽  
Author(s):  
Mao-Ze Wang ◽  
Ting-Wei Gu ◽  
Yang Xu ◽  
Lu Yang ◽  
Zhi-Hong Jiang ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Lipid Nanoparticles ◽  
Nucleic Acid Delivery ◽  
Mechanical Stretching

scholarly journals Development of nucleic acid delivery system using lipid nanoparticles

2016 ◽  
Vol 31 (1) ◽  
pp. 54-61
Author(s):  
Ayaka Okamoto ◽  
Tomohiro Asai ◽  
Naoto Oku
Keyword(s):  
Nucleic Acid ◽  
Delivery System ◽  
Lipid Nanoparticles ◽  
Nucleic Acid Delivery

scholarly journals State-of-the-Art Design and Rapid-Mixing Production Techniques of Lipid Nanoparticles for Nucleic Acid Delivery

Small Methods ◽  
2018 ◽  
Vol 2 (9) ◽  
pp. 1700375 ◽  
Author(s):  
Martijn J. W. Evers ◽  
Jayesh A. Kulkarni ◽  
Roy van der Meel ◽  
Pieter R. Cullis ◽  
Pieter Vader ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
State Of The Art ◽  
Lipid Nanoparticles ◽  
Nucleic Acid Delivery ◽  
Rapid Mixing ◽  
Production Techniques ◽  
Art Design

scholarly journals Cancer-targeted Nucleic Acid Delivery and Quantum Dot Imaging Using EGF Receptor Aptamer-conjugated Lipid Nanoparticles

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Min Woo Kim ◽  
Hwa Yeon Jeong ◽  
Seong Jae Kang ◽  
Moon Jung Choi ◽  
Young Myoung You ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Quantum Dot ◽  
Egf Receptor ◽  
Lipid Nanoparticles ◽  
Nucleic Acid Delivery

scholarly journals Complex Size and Surface Charge Determine Nucleic Acid Transfer by Fusogenic Liposomes

2020 ◽  
Vol 21 (6) ◽  
pp. 2244 ◽  
Author(s):  
Marco Hoffmann ◽  
Nils Hersch ◽  
Sven Gerlach ◽  
Georg Dreissen ◽  
Ronald Springer ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Surface Charge ◽  
Messenger Rna ◽  
Mammalian Cells ◽  
Nucleic Acid Delivery ◽  
Cell Cytoplasm ◽  
Delivery Methods ◽  
New Generation ◽  
Interfering Rna

Highly efficient, biocompatible, and fast nucleic acid delivery methods are essential for biomedical applications and research. At present, two main strategies are used to this end. In non-viral transfection liposome- or polymer-based formulations are used to transfer cargo into cells via endocytosis, whereas viral carriers enable direct nucleic acid delivery into the cell cytoplasm. Here, we introduce a new generation of liposomes for nucleic acid delivery, which immediately fuse with the cellular plasma membrane upon contact to transfer the functional nucleic acid directly into the cell cytoplasm. For maximum fusion efficiency combined with high cargo transfer, nucleic acids had to be complexed and partially neutralized before incorporation into fusogenic liposomes. Among the various neutralization agents tested, small, linear, and positively charged polymers yielded the best complex properties. Systematic variation of liposomal composition and nucleic acid complexation identified surface charge as well as particle size as essential parameters for cargo-liposome interaction and subsequent fusion induction. Optimized protocols were tested for the efficient transfer of different kinds of nucleic acids like plasmid DNA, messenger RNA, and short-interfering RNA into various mammalian cells in culture and into primary tissues.

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