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Non-Viral CRISPR carriers: transient delivery with lasting effects

Publications: Contribution to journalAnnotationPeer Reviewed

Abstract

CRISPR-Cas9 has revolutionized the field of genome editing. While conventional gene supplementation therapies and the market of related gene therapy products are dominated by viral vectors, non-viral delivery strategies are increasingly being explored for in vivo CRISPR applications. Given the permanent nature of genome editing, prolonged expression of the CRISPR machinery is not required, and transient delivery nevertheless can achieve lasting therapeutic effects. In contrast, short-term availability of genome editing components is rather considered advantageous to reduce the risk of off-target effects in a 'hit-and-run' fashion. In this article, we provide a systematic survey of the current clinical trial landscape with focus on in vivo CRISPR therapies and discuss utilized delivery strategies. As of December 2025, 136 CRISPR trials are ongoing, including 36 based on in vivo delivery of CRISPR components which show a clear shift towards non-viral vectors. The article describes the clinically employed CRISPR technologies and non-viral delivery platforms, highlighting both the present opportunities and key challenges associated with CRISPR delivery in the future.

Original languageEnglish
Article number2614125
JournalDrug Delivery
Volume33
Issue number1
DOIs
Publication statusPublished - 15 Jan 2026

Funding

FundersFunder number
Fonds zur Förderung der wissenschaftlichen Forschung (FWF)Grant DOI: 10.55776/PAT4833324

Austrian Fields of Science 2012

  • 301208 Pharmaceutical technology

Keywords

  • Humans
  • CRISPR-Cas Systems/genetics
  • Gene Editing/methods
  • Genetic Therapy/methods
  • Gene Transfer Techniques
  • Animals
  • Genetic Vectors
  • Clustered Regularly Interspaced Short Palindromic Repeats
  • CRISPR
  • genome editing
  • virus-like particles
  • lipid nanoparticles
  • clinical trials
  • non-viral delivery

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