# Advances in vehicles for in situ delivery: From classical vectors to biologically inspired structures

**Authors:** Hengyi Wang, Xiaoyan Tang, Xinyao Pan, Hongjie Tang, Jie Gao, Qi Li

PMC · DOI: 10.1016/j.synbio.2026.02.013 · 2026-03-17

## TL;DR

This review explores recent developments in delivery systems for proteins and nucleic acids, comparing viral and non-viral tools and highlighting new biologically inspired approaches.

## Contribution

The paper systematically reviews novel delivery systems like Arc, SEND, and Coacervate, offering insights into their mechanisms and potential for synthetic biology and gene therapy.

## Key findings

- Viral vectors like lentivirus and adeno-associated virus have high delivery efficiency but face challenges in immunogenicity and manufacturability.
- Non-viral tools such as lipid nanoparticles and exosomes offer safer alternatives but often lack sufficient delivery efficiency.
- Novel systems like Arc and Coacervate show promise due to their biologically inspired structures and functional versatility.

## Abstract

The emerging fields of synthetic biology and gene therapy rely on delivery systems to introduce the nucleic acids and proteins into recipient cells. Hence, the development of delivery tools with high specificity, strong manufacturability, and low immunogenicity can advance these fields. In this review, we summarize recent advances in the development of delivery systems for proteins and nucleic acids. First, we outline viral vector-based delivery tools, including lentivirus, adenovirus, and adeno-associated virus-based delivery technologies, discussing their advantages and limitations. Next, we summarize the advantages and disadvantages of non-viral vector-based delivery tools, including delivery strategies based on lipid nanoparticles, polyethyleneimine, exosomes, cell-penetrating peptides, virus-like particles, gold nanoparticles, and mesoporous silica nanoparticles. Lastly, we examine the specific principles and functional potential of novel delivery systems, including the Arc, PNMA2, SEND, PVC, and Coacervate systems. Overall, this review provides a systematic assessment of the mechanisms of action, current application progress, and future prospects for viral vectors, non-viral vectors, and novel delivery tools. Moreover, this review will serve as a reference for technological development and theoretical research in the fields of synthetic biology and gene therapy.

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## Full-text entities

- **Genes:** ARC (activity regulated cytoskeleton associated protein) [NCBI Gene 23237] {aka Arg3.1, hArc}, PNMA2 (PNMA family member 2) [NCBI Gene 10687] {aka MA2, MM2, RGAG2}
- **Chemicals:** polyethyleneimine (-), lipid (MESH:D008055), gold (MESH:D006046), silica (MESH:D012822)
- **Species:** Adenoviridae (family) [taxon 10508], Adeno-associated virus (species) [taxon 272636]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13011059/full.md

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Source: https://tomesphere.com/paper/PMC13011059