Exploring gold nanoparticles for RNA gene therapy

RNA-based therapeutics are a promising tool for gene therapy due to their ability to regulate gene and protein expression. Customized RNA strings can target the expression of specific problematic genes, treating a wide range of potential diseases.

However, RNA molecules are large and inherently unstable, which makes delivering them to the desired location in the body challenging. Modified viruses can be used as transporters for this purpose, but they can be targeted by the body’s immune system. As an alternative, ligand-functionalized metal nanoparticles can encapsulate the RNA molecule for safe delivery.

Nash et al. employed molecular dynamics simulations to study gold nanoparticles, one of the most common non-viral RNA delivery vectors. Their simulations tested a variety of properties to inform the next generation of nanoparticle designs.

One of the most crucial properties for nanoparticle delivery systems is the degree of compaction of the RNA inside. The more compact the assembly, the more stable it is, the longer it can survive in the body, and the greater its likelihood of reaching the desired target. The authors found a large metal core with short ligands to be the best arrangement for compacting RNA.

“This is the basic question for drug delivery systems: will the ‘pill’ reach the target organ safely, or will it just disintegrate as soon as it encounters some altered physiological conditions or other possible disturbances?” said author Alexey Gulyuk.

The team wants their simulations to benefit researchers building ligand-functionalized metal nanoparticles for gene delivery in the lab. They believe their work will make prototyping new designs faster and easier.

Source: “Gold nanoparticle design for RNA compaction,” by Jessica A. Nash, Matthew D. Manning, Alexey V. Gulyuk, Aleksey E. Kuznetsov, and Yaroslava G. Yingling, Biointerphases (2022). The article can be accessed at https://doi.org/10.1116/6.0002043 .

This paper is part of the Molecular Assembly at Biointerfaces Collection, learn more here .