Self-Assembled Plasmid Delivery System for PPM1D Knockout to Reverse Tumor Malignancy
Xiao-He Ren1, Xiao-Yan He1, Bo-Ya Liu1
1Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China.
ACS Applied Bio Materials
|January 12, 2022
Summary
This study developed a novel nanoparticle delivery system for CRISPR/Cas9 to knock out the PPM1D gene in cancer cells. This gene editing approach effectively suppressed tumor malignancy by inhibiting cancer cell proliferation, migration, and invasion.
Area of Science:
- Biotechnology
- Molecular Biology
- Cancer Research
Background:
- Gene delivery vectors are crucial for effective genome editing.
- The PPM1D gene is implicated in cancer malignancy.
- Targeting cancer-specific markers can improve therapeutic delivery.
Purpose of the Study:
- To design a multifunctional vector for CRISPR/Cas9 delivery.
- To achieve targeted knockout of the PPM1D gene in cancer cells.
- To evaluate the impact of PPM1D gene knockout on cancer malignancy.
Main Methods:
- Constructed nanoparticles encapsulating CRISPR/Cas9 plasmid.
- Utilized KALA peptide for endosomal escape and histones for nuclear transport.
- Decorated nanoparticles with hyaluronic acid (HA) and AS1411-incorporated HA (AHA) for CD44 and nucleolin targeting.
- Performed PPM1D gene knockout in cancer cells.
Main Results:
- Achieved efficient genome editing and PPM1D gene knockout.
- Demonstrated significant downregulation of PPM1D expression in targeted malignant cells.
- Observed altered expression of key proteins (p21, p-p38, cyclin D1, MMP9, CYR61, vimentin).
- Showcased suppressed proliferation, migration, and invasion of edited cancer cells.
Conclusions:
- The developed nanoparticle system enables targeted PPM1D gene knockout.
- PPM1D knockout effectively reverses tumor malignancy characteristics.
- This strategy holds promise for cancer therapy through genome editing.
