We are delighted to share the news that, as of 11th June 2026, the (EU Standards related) Collaborative Workshop Agreement CWA 18386:2026 - Determination of nucleic acid encapsulation efficiency in Lipid Nanoparticles using fluorometry is available and freely accessible to anyone on the CEN open-access CWA download area.

Use this link to browse the CWA download area of the CEN website, or

Directly download the open access CWA 1836:2026

Background and Further Information

Lipid nanoparticles (LNPs) have emerged in recent years as a powerful platform for the delivery of nucleic acids, gaining increasing relevance in both academic research and clinical applications. Their successful use in mRNA-based vaccines and gene therapies has accelerated the need for reliable characterization tools that ensure the safety, efficacy, and reproducibility of LNP-based formulations. Among the key parameters influencing the performance of these systems, encapsulation efficiency plays a critical role, as it directly affects protection from enzymatic degradation, intracellular delivery, and therapeutic potency.

Currently, several analytical techniques are employed to estimate the encapsulation efficiency of RNA and DNA within LNPs. These include gel electrophoresis, UV absorbance, and dynamic light scattering (DLS). While commonly used, these methods suffer from important limitations such as low sensitivity, interference from free nucleic acids, and inability to distinguish encapsulated from non-encapsulated species with sufficient accuracy.

The aim of this CWA is therefore to define a robust and reproducible fluorometric protocol for the determination of RNA and DNA encapsulation efficiency in lipid nanoparticles. Its scope is strictly analytical and does not extend to LNP formulation design, in vivo performance, or therapeutic evaluation.

This CWA was developed within the framework of the EU ETERNAL Project, which identified the lack of standardization in this area as a major barrier to the development of reproducible and scalable delivery systems. The resulting protocol is intended to support research laboratories, pharmaceutical developers, and biotechnology companies in the harmonization of analytical practices, enabling more efficient and comparable product development pipelines.