Near-infrared upconversion-activated CRISPR-Cas9 system: A remote-controlled gene editing platform

Area of Science:

• Biotechnology
• Nanomedicine
• Molecular Biology

Background:

• CRISPR-Cas9 is a powerful genome editing tool but faces challenges in controlled delivery.
• Spatiotemporal control of CRISPR-Cas9 is crucial for effective gene editing therapies.
• Existing methods lack precision in targeting and delivery, especially in vivo.

Purpose of the Study:

• To design a near-infrared (NIR) light-responsive nanocarrier for controlled CRISPR-Cas9 delivery.
• To develop a novel cancer therapeutic strategy using light-activated gene editing.
• To demonstrate the efficacy of NIR-activated CRISPR-Cas9 for inhibiting tumor cell proliferation.

Main Methods:

• Utilized upconversion nanoparticles (UCNPs) as NIR light-responsive nanocarriers.
• Engineered UCNPs to convert NIR light into UV light for controlled CRISPR-Cas9 release.
• Designed a single guide RNA targeting the polo-like kinase-1 (PLK-1) tumor gene.
• Validated the system's efficacy in vitro and in vivo tumor models.

Main Results:

• Successfully developed NIR light-triggered CRISPR-Cas9 release from UCNPs.
• Demonstrated NIR light-activated gene editing of PLK-1 in tumor cells.
• Achieved significant inhibition of tumor cell proliferation both in vitro and in vivo.
• Showcased precise spatiotemporal control over gene editing with NIR light.

Conclusions:

• The NIR light-responsive nanocarrier system offers precise, on-demand CRISPR-Cas9 delivery.
• This technology holds significant potential for targeted cancer therapeutics and deep-tissue gene editing.
• Exogenously controlled gene editing presents a promising avenue for treating various diseases.