Note: Innovative Precision Gene-Editing Tools in Personalized Cancer Medicine

Note: Innovative Precision Gene-Editing Tools in Personalized Cancer Medicine

doi: 10.1002/advs.201902552


Overview of gene editing applications



Application;

  • Discovery of Cancer Driver Genes Using Gene-Editing Tools -- library screening

  • Targeted Delivery Systems for Genome and Epigenome-Editing

  • Establishment of Animal Models for Cancer Target Validation Using Gene-Editing Tools

  • EpiGenome Engineering in Cancer Cells -- using gRNA+genetic engineered CAS9+fused epigenome manipulated enzyme

  • Clinical Applications of Gene-Editing Tools -- immunotherapy

  • Applications of Gene-Editing Tools in Cancer Treatment Generation of Universal T Cells for Cancer Immunotherapy

  • Enhancement of T Cells’ Functionalities in Cancer Immunotherapy

  • Editing of Cancer Driver Genes in Cancer Therapy

  • Applications of Gene-Editing Tools in Cancer Prevention


Challenges:

Technical issues

  • Restricted genomic target sites by sgRNA

    • Require improvement on sgRNA design to improve target efficiency

    • Structural characteristic of sgRNA effect Cas9 activity

    • Cas9 from different bacterial species recognized different PAM

  • CRISPR/Cas9 induces p53 activation due to DSB repair -- advantageous for treating cancer harboring p53 mutation (thus, the cell can repair genetic material through DSB, wt-p53 cancer cells could not perform this function -- bc it can DSB can trigger apoptosis through p53 function) 

  • Alternative approach for p53-wt -- > genetic engineering Cas9 -- > to become nickase (cut one strand of DNA) -- > and make use the other DNA repair enzymes to correct the gene (this approach avoid DSB and does require the donor template) -- efficient in “post-mitotic cells with reduced HDR”

  • Off-target in gene editing

  • Ethic concern -- equity in population


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