# Evaluation of Peptide Nucleic Acid Encapsulation in Ferritin Nanocages for Gene Silencing Applications

## TL;DR

Researchers showed that peptide nucleic acids can be effectively encapsulated in a ferritin nanocage to improve their delivery into cells for gene silencing.

## Contribution

A new method for encapsulating PNAs in a polycationic ferritin system is demonstrated, enabling efficient gene silencing in cancer cells.

## Key findings

- PNAs were successfully loaded into the PA3.2-HumAfFt bioconjugate using a divalent-cation-triggered method.
- Encapsulated PNAs showed effective uptake and gene silencing in cancer cells, particularly targeting the GAPDH gene.

## Abstract

Peptide nucleic acids
(PNAs) feature a neutral peptide-like backbone,
providing nuclease resistance and potential for precision medicine
and diagnostics through specific DNA and RNA binding. However, their
therapeutic use is hindered by poor solubility and cell permeability.
In this study, we demonstrated that negatively charged PNAs can be
readily loaded into the polycationic Humanized Archaeoglobus Ferritin,
namely, PA3.2-HumAfFt bioconjugate system, following a divalent-cation-triggered
oligomerization technique. The versatility of PNA chemistry enabled
the production of synthetic nucleic acid homologues with varying lengths
and charges, ranging from positive to negative. We evaluated the loading
performance of HumAfFt with and without chemical modifications and
investigated the release dynamics of PNAs under conditions simulating
the intracellular environment. Our findings demonstrated the effective
uptake, release, and biological activity of PNAs in cancer cells,
notably silencing the GAPDH gene with good efficiency. This evaluation
paves the way for optimizing PNA-based therapeutics and broadening
their applications.