Precise cancer cell targeting by CRISPR-Cas9 is now possible according to the article published by South Korean researchers.
The targeted killing of cancer cells without affecting surrounding normal cells is the most desirable approach for cancer therapy. However, this cannot be easily achieved, owing to the shared properties of normal and cancer cells.
DNA damaging agents that inhibit DNA replication have been used as part of many conventional cancer therapies, including radiation and chemotherapeutic regimens. However, these treatments also damage the DNA in neighboring healthy cells, which then causes undesirable side effects including cell death and mutations.
Scientists have long been searching for a method to selectively target only cancer cells without affecting normal cells, which is a crucial requirement for ideal cancer therapy. In this study, the researchers developed a therapeutic strategy called the cancer-specific insertions–deletions (InDels) attacker (CINDELA). This strategy selectively induces cancer cell death using the CRISPR-Cas system.
CINDELA utilizes a previously unexplored idea of introducing CRISPR-mediated DNA double-strand breaks (DSBs) in a cancer-specific fashion to facilitate specific cell death. Cancer genomics projects have found that regardless of their origins, most cancer cells accumulate many mutations including small insertion/deletion (InDel) of several nucleotides. CINDELA targets multiple InDels with CRISPR-Cas9 to produce many DNA DSBs that result in cancer-specific cell death.
As a proof of concept, the researchers demonstrated that CINDELA selectively kills human cancer cell lines, xenograft human tumors in mice, patient-derived glioblastoma, and lung patient-driven xenograft tumors without affecting healthy human cells or altering mouse growth.
Source: Taejoon Kwon et al. Precision targeting tumor cells using cancer-specific InDel mutations with CRISPR-Cas9.
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