A Multifunction Lipid-Based CRISPR-Cas13a Genetic Circuit Delivery System for Bladder Cancer Gene Therapy

Jing Fan1,2,3, Yuchen Liu1, Lisa Liu1

  • 1Department of Urology, Shenzhen Second People's Hospital , The First Affiliated Hospital of Shenzhen University , Shenzhen 518039 , China.

ACS Synthetic Biology
|January 1, 2020
PubMed

Insights

This study introduces a novel liposome system for CRISPR-Cas13a gene therapy in bladder cancer. The system targets tumor cells, offers controlled gene editing, and enhances therapeutic outcomes for bladder cancer treatment.

Area of Science:

  • Oncology
  • Gene Therapy
  • Nanotechnology

Background:

  • Bladder cancer treatment options are limited, necessitating novel therapeutic strategies.
  • Gene therapy, particularly using CRISPR-Cas13a, presents a promising avenue for targeted cancer treatment.

Purpose of the Study:

  • To develop and evaluate a versatile liposome delivery system for CRISPR-Cas13a gene circuits in bladder cancer.
  • To assess the efficacy and safety of this system for targeted gene editing in bladder cancer cells.

Main Methods:

  • Development of a liposome system for CRISPR-Cas13a gene delivery.
  • In vitro studies and intravesical perfusion studies in mice.
  • Incorporation of hVEGFR2 targeting, tumor-specific promoters, near-infrared photosensitizers, and multiple crRNA sequences.

Main Results:

  • CRISPR-Cas13a demonstrated gene expression editing without compromising genome stability.
  • Liposomes effectively targeted hVEGFR2-expressing bladder cancer cells.
  • Near-infrared light controlled the release of the photosensitizer for targeted delivery.
  • Multi-crRNA sequences enabled broader therapeutic effects.

Conclusions:

  • The developed liposome system offers a versatile strategy for CRISPR-Cas13a-based gene therapy in bladder cancer.
  • This approach combines targeted delivery, controlled gene editing, and enhanced therapeutic potential.