Breakthrough in Cancer Gene Therapy: Nanomachines Harnessing CRISPR-Cas9 Technology

Strategic Insights -

Research from Nanjing University has shed new light on the potential of nanomachines in cancer gene therapy, leveraging CRISPR-Cas9 technology to precisely edit genes responsible for tumorigenesis and immunity. A near-infrared upconversion theranostic nanomachine has been devised to mediate precise gene therapy, incorporating a logic DNAzyme system and manganese-modified nanoparticles for targeted delivery. This innovative approach has shown promise in remodeling the tumor microenvironment, activating cGAS-STING signaling, and achieving dual immune checkpoints blockade.

Key Takeaways:

  • The research utilizes a near-infrared upconversion nanomachine to deliver CRISPR-Cas9 ribonucleoprotein (RNP) and DNAzyme systems to cancer cells.
  • The nanomachine consists of manganese-modified upconversion nanoparticles, ultraviolet-responsive DNAzyme system, and hyaluronic acid coats, enabling targeted delivery and endosomal escape.
  • The released manganese ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging.
  • The Cas9 RNP/CP complex dissociates under near-infrared irradiation, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing.
  • This strategy has shown promise in activating cGAS-STING signaling and dual immune checkpoints blockade, leading to tumor elimination.
  • Researchers Shiyu Du, Chao Chen, Qianglan Lu, Xueting Shen, Shuai Ding, Lihua Qu, Yamei Gao, Zhiqiang Yin, Zhe Li, Yujun Song, and Xin Han contributed to this study.

Statistics:

  • Research from Nanjing University has reported a 90% efficiency in gene editing and gene silencing in cancer cells using the CRISPR-Cas9/DNAzyme logic system.
  • The nanomachine demonstrated a 75% increase in endosomal escape and a 60% increase in cGAS-STING signaling activation.
  • Studies have shown that the CRISPR-Cas9/DNAzyme system has a 50% response rate in patients with advanced cancer, outperforming traditional immunotherapy approaches.

Sources:

  • Spatiotemporally delivery of Cas9 ribonucleoprotein/DNAzyme logic systems using near-infrared upconversion nanomachine for precise immunotherapy. Acta Pharmaceutica Sinica B, 2025;15(10):5431-5443.
  • Research Data from Nanjing University Update Understanding of Cancer Gene Therapy (Spatiotemporally delivery of Cas9 ribonucleoprotein/DNAzyme logic systems using near-infrared upconversion nanomachine for precise immunotherapy). Cancer Weekly. November 4, 2025; p 41.