Cell-Type-Specific CRISPR/Cas9 Delivery by Biomimetic Metal Organic Frameworks

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Gene Editing

Background:

• Effective and cell-type-specific delivery of CRISPR/Cas9 gene editing tools is crucial for therapeutic applications.
• Current delivery methods face challenges in achieving precise targeting and avoiding off-target effects.

Purpose of the Study:

• To develop a biomimetic platform for targeted and cell-specific delivery of CRISPR/Cas9 gene editing machinery.
• To create cancer cell membrane-coated zeolitic imidazolate frameworks (ZIFs) for enhanced delivery.

Main Methods:

• Zeolitic imidazolate frameworks (ZIF-8) were loaded with CRISPR/Cas9 (CC-ZIF).
• CC-ZIF was coated with cancer cell membranes to create C³-ZIF(cell membrane type).
• Cellular uptake and genome editing efficiency were evaluated in various cell lines (MCF-7, HeLa, HDFn, aTC) and in vivo.

Main Results:

• C³-ZIF(MCF) demonstrated highest uptake in MCF-7 cancer cells with negligible uptake in healthy cells (HDFn, aTC).
• Transfection with C³-ZIF(MCF) resulted in a 3-fold repression of EGFP expression in MCF-7 cells.
• In vivo studies confirmed selective accumulation of C³-ZIF(MCF) in MCF-7 tumors.

Conclusions:

• The biomimetic C³-ZIF platform enables highly specific cancer cell targeting and gene editing.
• This approach addresses the critical need for cell-specific delivery in advancing genome editing technologies.
• This strategy holds significant potential for future clinical translation of gene editing therapies.