Gene Editing in Cancer Therapy and Antiviral Research: Recent Advances and Applications

Gene Editing
Gene Editing

Gene Editing in Cancer Therapy and Antiviral Research: Recent Advances and Applications (as of May 2025)

I. Cancer Therapy: Revolutionizing Treatment Paradigms

Gene editing technologies (e.g., CRISPR-Cas9, Prime Editing, Base Editing) are reshaping cancer treatment by targeting oncogenes, modulating the immune system, and optimizing existing therapies. Key advancements include:

1. Targeting Oncogenes and Tumor Suppressors

  • Oncogene Silencing:
    CRISPR-Cas9 knocks out oncogenic mutations (e.g., KRAS, EGFR, MYC), suppressing tumor growth. Prime Editing has corrected TP53 mutations, restoring tumor-suppressive functions and inducing regression in pancreatic cancer models.
  • Epigenetic Regulation:
    CRISPR/dCas9 fused with epigenetic modifiers (e.g., DNMT3A, HDAC) silences oncogenes. Targeting BRCA1 promoter methylation reverses chemotherapy resistance in ovarian cancer.

2. Enhancing Immunotherapy

  • CAR-T Cell Engineering:
    • Dual-Targeting CAR-T: Simultaneously targeting CD19 and CD22 reduces relapse rates in B-cell leukemia (Phase II trial: 85% complete remission rate).
    • Armored CAR-T: Inserting IL-12 or PD-1 antibody genes enhances tumor microenvironment penetration, extending progression-free survival in glioblastoma by >6 months.
  • Reversing T-Cell Exhaustion: Knocking out TET2 or overexpressing c-Jun revitalizes exhausted T cells.

3. Oncolytic Viruses and Gene Therapy

  • Engineered HSV-1: Deletion of the ICP34.5 gene reduces neurotoxicity, while inserting GM-CSF enhances immune response (Phase III melanoma trial: 62% objective response rate).
  • Conditionally Replicating Adenoviruses: Tumor-specific promoters (e.g., hTERT) control viral replication, targeting lung cancer while sparing healthy tissue.

4. Personalized Precision Therapy

  • Multi-Omics-Driven Editing: Patient-specific CRISPR libraries, informed by single-cell sequencing, target heterogeneous clones in lung cancer.
  • Nanoparticle Delivery Systems: Lipid nanoparticles (LNPs) loaded with CRISPR components achieve 90% KRAS mutation knockout in mouse models via EGFR-targeted delivery.

5. Overcoming Drug Resistance

  • Gene Editing + Chemotherapy: Knocking out ABCB1 (multidrug resistance gene) increases ovarian cancer sensitivity to paclitaxel by 10-fold.
  • Reversible CRISPR Systems: Cas13 RNA editing with small-molecule switches controls oncogene silencing duration, minimizing off-target risks.

II. Antiviral Research: Direct and Host-Focused Strategies

Gene editing combats viruses by directly targeting viral genomes or enhancing host immunity, with breakthroughs in HIV, HPV, and emerging pathogens:

1. Direct Viral Genome Targeting

  • HIV Latent Reservoir Clearance: CRISPR-Cas9 targets HIV proviral LTR regions, eliminating 90% of latent reservoirs in primate models.
  • HPV Cancer Prevention: AAV-delivered CRISPR systems disrupt HPV16/18 E6/E7 oncogenes in cervical cells, blocking carcinogenesis.

2. Host Gene Engineering

  • CCR5 Knockout: Base Editing introduces the CCR5Δ32 mutation into CD4+ T cells, conferring HIV resistance (Phase I: 99% viral load reduction).
  • Interferon Pathway Activation: Editing STAT1 boosts type I interferon signaling, suppressing influenza and SARS-CoV-2 replication in vitro.

3. Addressing Emerging Viruses

  • Broad-Spectrum Antivirals: Programmable CRISPR systems (e.g., Cas12b) target conserved viral sequences (e.g., coronavirus ORF1ab) for rapid adaptation to new strains.
  • Attenuated Viral Vectors: Deleting virulence genes (e.g., HSV-1 ICP47) creates safer vaccine platforms.

III. Innovations and Clinical Translation

1. Next-Gen Editing Tools

  • Prime Editing: Corrects single-base mutations without double-strand breaks, validated in lung and breast cancer.
  • Epigenome Editing: CRISPR/dCas9-TET1 demethylates and reactivates tumor suppressors, avoiding DNA damage.

2. Delivery Breakthroughs

  • Exosome Delivery: Engineered exosomes carry Cas9 mRNA across the blood-brain barrier for glioma therapy.
  • In Vivo Editing: LNP-encapsulated base editors achieve >80% sustained PCSK9 silencing in mouse hepatocytes.

3. Challenges and Ethics

  • Off-Target Control: AI tools (e.g., DeepCRISPR) reduce off-target rates from 1% to <0.1%.
  • Accessibility and Equity: Open-source platforms (e.g., OpenPrime) lower costs, but global regulatory harmonization remains critical.

IV. Future Directions

  • Multi-Omics Integration: Combine genomic, proteomic, and metabolomic data for multi-layered editing strategies.
  • Real-Time Dynamic Control: Optogenetic or chemically induced CRISPR systems enable precise therapeutic dosing.
  • Antiviral-Cancer Synergy: Oncolytic viruses carrying anti-HIV genes target both tumors and latent infections.

Conclusion

Gene editing drives personalized breakthroughs in cancer therapy through precision targeting and immune enhancement, while antiviral applications span direct viral genome disruption to host immunity engineering. As Prime Editing and epigenome editing mature, clinical translation will accelerate, though safety, accessibility, and ethical challenges demand global collaboration.

Data sourced from publicly available references. Contact: chuanchuan810@gmail.com.

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