BioInsights - How are cationic lipids offering new possibilities in the delivery of RNA therapeutics?
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How are cationic lipids offering new possibilities in the delivery of RNA therapeutics?

How are cationic lipids offering new possibilities in the delivery of RNA therapeutics?

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Ionizable lipid nanoparticles (LNPs) have been widely used for in vivo delivery of RNA therapeutics, predominantly ending up targeting the liver (Patisiran, BNTech162b, mRNA-1273). The current challenge in the use of commercially available lipids is to have a better control over the biodistribution of the RNA once delivered systemically to target different organs and cell types.

Novel lipidic formulations using different ionizable cationic lipids were characterized by DLS to assess size and zeta potential and mRNA encapsulation efficiency was assessed by the RiboGreen assay. Novel lipidic formulations were tested for mRNA delivery both in vitro and in vivo though intra-veinous and intramuscular injections to evaluate their stability, efficacy and biodistribution. Here we demonstrate that our proprietary cationic lipid is key to developing lipid nanoparticles that can deliver mRNA to different cell lines and organs. mRNA delivery efficacy was first evaluated in vitro in different cell lines, and human primary immune cells. Secondly, we evaluated in vivo biodistribution using both systemic and local administration routes (respectively intra-veinous and intramuscular). In vivo transfection efficiency was assessed by luciferase expression in a mouse model. Following systemic injection of our novel lipidic formulations, we could measure luciferase expression in not only lung and liver, but also in spleen, kidney, heart and pancreas. Furthermore, with a local intramuscular injection, the luciferase expression was well restricted to the injected muscle.

Our novel proprietary cationic lipid removes the current limitation of LNPs to target different organs and cell types. Our novel lipidic formulations ensure the same efficacy as LNPs with ionizable lipids, whilst ensuring better biodistribution to target organs other than liver and lung.

Maria Nicla Loviglio, PhD

Scientific Support Specialist, Polyplus-transfection

Nicla completed her MSc. at the University of Bari (Italy) and obtained her PhD in Integrative Experimental and Computational Biology at the University of Lausanne (Switzerland). Prior to joining Polyplus-transfection, she worked as visiting scientist at the Center for Human Disease Modeling (Duke University, US) and as a postdoctoral researcher at the Institut de Génétique et de Biologie Moléculaire et Cellulaire (France), where she investigated the impact of gene dosage defects on basic neurodevelopmental processes using the developing zebrafish as an in vivo model.

Malik Hellal, PhD

Head of R&D Chemistry, Polyplus-transfection 

Malik obtained his Ph.D. in Organic and Medicinal chemistry from the University of Strasbourg. Prior to joining Polyplus, Malik had a post-doctoral experience at Harvard NeuroDiscovery Center, followed by a Marie Curie fellow position at the Institute of Supramolecular Science and Engineering (ISIS). Malik is an expert in the conception and synthesis of polymers and lipids for the development of innovative targeted delivery solutions.


Malik Hellal
Malik Hellal
Senior Scientist, Chemistry at Polyplus-transfection
Maria Nicla Loviglio
Maria Nicla Loviglio
Scientific Support Specialist at Polyplus-transfection

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