Targeting HPV16 DNA using CRISPR/Cas inhibits anal cancer growth in vivo

Area of Science:

• Molecular Biology
• Gene Therapy
• Oncology

Background:

• Human papillomavirus (HPV) is a major cause of cervical and anal cancers.
• HPV16 oncoproteins E6 and E7 are critical for tumor development.
• Targeting these oncoproteins presents a potential therapeutic strategy.

Purpose of the Study:

• To evaluate the efficacy of a single adeno-associated virus (AAV) vector delivering CRISPR-Cas9 and specific guide RNAs (gRNAs) against HPV16 E6 and E7 genes.
• To determine if this approach can inhibit HPV16-induced tumor growth in vivo.

Main Methods:

• Patient-derived, HPV16-positive anal cancer explants were xenografted into immunodeficient mice.
• Mice bearing these tumors were injected with AAV vectors encoding Cas9 and either control or HPV16-specific gRNAs.

Main Results:

• Targeting the HPV16 E6 and E7 genes with CRISPR-Cas9 resulted in a significant and selective reduction in tumor growth.
• Control vectors did not show a similar inhibitory effect.

Conclusions:

• CRISPR-Cas gene editing targeting HPV16 E6/E7 demonstrates significant anti-tumor activity in vivo.
• This study provides proof of principle for using CRISPR/Cas as a selective therapy for HPV-induced tumors in humans.