INTERNATIONAL CONGRESS OF
CancerGenetics
CRISPR-Based Genome Editing for the Treatment of Genetic Disorders and Cancer
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kimiya kazemi esfeh,1,*
1. 3Department of Microbiology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Introduction: Genome editing allows for the targeted modification of DNA within living cells. Among several genome editing platforms, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas systems have garnered significant attention due to their simplicity, programmability, and efficiency. Derived from bacterial adaptive immunity, CRISPR/Cas9 has rapidly evolved into a powerful biomedical tool. The advent of CRISPR technology has profound implications for the treatment of human diseases. In particular, the ability to correct pathogenic mutations or disrupt oncogenic genes has paved the way for novel therapeutic strategies against inherited disorders and cancer. Genome editing allows for the targeted modification of DNA within living cells. Among several genome editing platforms, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas systems have garnered significant attention due to their simplicity, programmability, and efficiency. Derived from bacterial adaptive immunity, CRISPR/Cas9 has rapidly evolved into a powerful biomedical tool. The advent of CRISPR technology has profound implications for the treatment of human diseases. In particular, the ability to correct pathogenic mutations or disrupt oncogenic genes has paved the way for novel therapeutic strategies against inherited disorders and cancer. Genome editing allows for the targeted modification of DNA within living cells. Among several genome editing platforms, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas systems have garnered significant attention due to their simplicity, programmability, and efficiency. Derived from bacterial adaptive immunity, CRISPR/Cas9 has rapidly evolved into a powerful biomedical tool. The advent of CRISPR technology has profound implications for the treatment of human diseases. In particular, the ability to correct pathogenic mutations or disrupt oncogenic genes has paved the way for novel therapeutic strategies against inherited disorders and cancer. Genome editing allows for the targeted modification of DNA within living cells. Among several genome editing platforms, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas systems have garnered significant attention due to their simplicity, programmability, and efficiency. Derived from bacterial adaptive immunity, CRISPR/Cas9 has rapidly evolved into a powerful biomedical tool. The advent of CRISPR technology has profound implications for the treatment of human diseases. In particular, the ability to correct pathogenic mutations or disrupt oncogenic genes has paved the way for novel therapeutic strategies against inherited disorders and cancer. Genome editing allows for the targeted modification of DNA within living cells. Among several genome editing platforms, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas systems have garnered significant attention due to their simplicity, programmability, and efficiency. Derived from bacterial adaptive immunity, CRISPR/Cas9 has rapidly evolved into a powerful biomedical tool. The advent of CRISPR technology has profound implications for the treatment of human diseases. In particular, the ability to correct pathogenic mutations or disrupt oncogenic genes has paved the way for novel therapeutic strategies against inherited disorders and cancer. Genome editing allows for the targeted modification of DNA within living cells. Among several genome editing platforms, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas systems have garnered significant attention due to their simplicity, programmability, and efficiency. Derived from bacterial adaptive immunity, CRISPR/Cas9 has rapidly evolved into a powerful biomedical tool. The advent of CRISPR technology has profound implications for the treatment of human diseases. In particular, the ability to correct pathogenic mutations or disrupt oncogenic genes has paved the way for novel therapeutic strategies against inherited disorders and cancer. Genome editing allows for the targeted modification of DNA within living cells. Among several genome editing platforms, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas systems have garnered significant attention due to their simplicity, programmability, and efficiency. Derived from bacterial adaptive immunity, CRISPR/Cas9 has rapidly evolved into a powerful biomedical tool. The advent of CRISPR technology has profound implications for the treatment of human diseases. In particular, the ability to correct pathogenic mutations or disrupt oncogenic genes has paved the way for novel therapeutic strategies against inherited disorders and cancer. Genome editing allows for the targeted modification of DNA within living cells. Among several genome editing platforms, CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas systems have garnered significant attention due to their simplicity, programmability, and efficiency. Derived from bacterial adaptive immunity, CRISPR/Cas9 has rapidly evolved into a powerful biomedical tool. The advent of CRISPR technology has profound implications for the treatment of human diseases. In particular, the ability to correct pathogenic mutations or disrupt oncogenic genes has paved the way for novel therapeutic strategies against inherited disorders and cancer.
- Methods: vvOncogene Targeting CRISPR allows inactivation of key oncogenes such as KRAS, MYC, and BCL2 in vitro and in vivo, offering insights into tumor dependency. 4.2 Immunotherapy Enhancement CRISPR is being used to engineer T cells for enhanced tumor killing: • PD-1 knockout: Increases T cell cytotoxicity. • CAR-T cells: Engineered with CRISPR to increase specificity and resistance to exhaustion. 4.3 Synthetic Lethality Screens CRISPR-based screens help identify cancer-specific vulnerabilities, facilitating the discovery of novel drug targets. 5. Delivery Systems Efficient and safe delivery remains a major bottleneck for in vivo CRISPR therapy. Various platforms include: • Viral Vectors: AAV and lentiviruses (high efficiency, but immunogenicity concerns). • Lipid Nanoparticles (LNPs): Non-viral and biocompatible; used in mRNA COVID vaccines. • Electroporation/Nucleofection: For ex vivo editing of hematopoietic stem cells or T cells. 6. Ethical and Safety Considerations • Off-target Effects: Unintended DNA cleavage may lead to genotoxicity. • Germline Editing: Raises profound ethical concerns; currently banned in most countries. • Equity of Access: High cost and infrastructure requirements may limit availability. The 2018 "CRISPR babies" scandal in China underscored the urgency for stringent global regulation. Oncogene Targeting CRISPR allows inactivation of key oncogenes such as KRAS, MYC, and BCL2 in vitro and in vivo, offering insights into tumor dependency. 4.2 Immunotherapy Enhancement CRISPR is being used to engineer T cells for enhanced tumor killing: • PD-1 knockout: Increases T cell cytotoxicity. • CAR-T cells: Engineered with CRISPR to increase specificity and resistance to exhaustion. 4.3 Synthetic Lethality Screens CRISPR-based screens help identify cancer-specific vulnerabilities, facilitating the discovery of novel drug targets. 5. Delivery Systems Efficient and safe delivery remains a major bottleneck for in vivo CRISPR therapy. Various platforms include: • Viral Vectors: AAV and lentiviruses (high efficiency, but immunogenicity concerns). • Lipid Nanoparticles (LNPs): Non-viral and biocompatible; used in mRNA COVID vaccines. • Electroporation/Nucleofection: For ex vivo editing of hematopoietic stem cells or T cells. 6. Ethical and Safety Considerations • Off-target Effects: Unintended DNA cleavage may lead to genotoxicity. • Germline Editing: Raises profound ethical concerns; currently banned in most countries. • Equity of Access: High cost and infrastructure requirements may limit availability. The 2018 "CRISPR babies" scandal in China underscored the urgency for stringent global regulation. Oncogene Targeting CRISPR allows inactivation of key oncogenes such as KRAS, MYC, and BCL2 in vitro and in vivo, offering insights into tumor dependency. 4.2 Immunotherapy Enhancement CRISPR is being used to engineer T cells for enhanced tumor killing: • PD-1 knockout: Increases T cell cytotoxicity. • CAR-T cells: Engineered with CRISPR to increase specificity and resistance to exhaustion. 4.3 Synthetic Lethality Screens CRISPR-based screens help identify cancer-specific vulnerabilities, facilitating the discovery of novel drug targets. 5. Delivery Systems Efficient and safe delivery remains a major bottleneck for in vivo CRISPR therapy. Various platforms include: • Viral Vectors: AAV and lentiviruses (high efficiency, but immunogenicity concerns). • Lipid Nanoparticles (LNPs): Non-viral and biocompatible; used in mRNA COVID vaccines. • Electroporation/Nucleofection: For ex vivo editing of hematopoietic stem cells or T cells. 6. Ethical and Safety Considerations • Off-target Effects: Unintended DNA cleavage may lead to genotoxicity. • Germline Editing: Raises profound ethical concerns; currently banned in most countries. • Equity of Access: High cost and infrastructure requirements may limit availability. The 2018 "CRISPR babies" scandal in China underscored the urgency for stringent global regulation. Oncogene Targeting CRISPR allows inactivation of key oncogenes such as KRAS, MYC, and BCL2 in vitro and in vivo, offering insights into tumor dependency. 4.2 Immunotherapy Enhancement CRISPR is being used to engineer T cells for enhanced tumor killing: • PD-1 knockout: Increases T cell cytotoxicity. • CAR-T cells: Engineered with CRISPR to increase specificity and resistance to exhaustion. 4.3 Synthetic Lethality Screens CRISPR-based screens help identify cancer-specific vulnerabilities, facilitating the discovery of novel drug targets. 5. Delivery Systems Efficient and safe delivery remains a major bottleneck for in vivo CRISPR therapy. Various platforms include: • Viral Vectors: AAV and lentiviruses (high efficiency, but immunogenicity concerns). • Lipid Nanoparticles (LNPs): Non-viral and biocompatible; used in mRNA COVID vaccines. • Electroporation/Nucleofection: For ex vivo editing of hematopoietic stem cells or T cells. 6. Ethical and Safety Considerations • Off-target Effects: Unintended DNA cleavage may lead to genotoxicity. • Germline Editing: Raises profound ethical concerns; currently banned in most countries. • Equity of Access: High cost and infrastructure requirements may limit availability. The 2018 "CRISPR babies" scandal in China underscored the urgency for stringent global regulation.
- Results: vvvvEmerging CRISPR variants such as base editors and prime editors allow precise DNA/RNA editing without inducing DSBs, minimizing cellular stress and off-target risks. Multiplexed editing, RNA-targeting Cas13 systems, and all-in-one delivery platforms promise broader applicability. Clinical trials using CRISPR are expanding, with ex vivo and in vivo trials for hemoglobinopathies, cancers, and eye diseases showing promising early results. Emerging CRISPR variants such as base editors and prime editors allow precise DNA/RNA editing without inducing DSBs, minimizing cellular stress and off-target risks. Multiplexed editing, RNA-targeting Cas13 systems, and all-in-one delivery platforms promise broader applicability. Clinical trials using CRISPR are expanding, with ex vivo and in vivo trials for hemoglobinopathies, cancers, and eye diseases showing promising early results. Emerging CRISPR variants such as base editors and prime editors allow precise DNA/RNA editing without inducing DSBs, minimizing cellular stress and off-target risks. Multiplexed editing, RNA-targeting Cas13 systems, and all-in-one delivery platforms promise broader applicability. Clinical trials using CRISPR are expanding, with ex vivo and in vivo trials for hemoglobinopathies, cancers, and eye diseases showing promising early results. Emerging CRISPR variants such as base editors and prime editors allow precise DNA/RNA editing without inducing DSBs, minimizing cellular stress and off-target risks. Multiplexed editing, RNA-targeting Cas13 systems, and all-in-one delivery platforms promise broader applicability. Clinical trials using CRISPR are expanding, with ex vivo and in vivo trials for hemoglobinopathies, cancers, and eye diseases showing promising early results. Emerging CRISPR variants such as base editors and prime editors allow precise DNA/RNA editing without inducing DSBs, minimizing cellular stress and off-target risks. Multiplexed editing, RNA-targeting Cas13 systems, and all-in-one delivery platforms promise broader applicability. Clinical trials using CRISPR are expanding, with ex vivo and in vivo trials for hemoglobinopathies, cancers, and eye diseases showing promising early results. Emerging CRISPR variants such as base editors and prime editors allow precise DNA/RNA editing without inducing DSBs, minimizing cellular stress and off-target risks. Multiplexed editing, RNA-targeting Cas13 systems, and all-in-one delivery platforms promise broader applicability. Clinical trials using CRISPR are expanding, with ex vivo and in vivo trials for hemoglobinopathies, cancers, and eye diseases showing promising early results. Emerging CRISPR variants such as base editors and prime editors allow precise DNA/RNA editing without inducing DSBs, minimizing cellular stress and off-target risks. Multiplexed editing, RNA-targeting Cas13 systems, and all-in-one delivery platforms promise broader applicability. Clinical trials using CRISPR are expanding, with ex vivo and in vivo trials for hemoglobinopathies, cancers, and eye diseases showing promising early results.
- Conclusion: vCRISPR genome editing has revolutionized our ability to treat genetic disorders and cancer at their root cause. While significant technical and ethical challenges remain, ongoing advances in delivery, editing precision, and clinical trial design continue to bring this technology closer to widespread clinical use. With responsible development and global oversight, CRISPR holds transformative potential for 21st-century medicine.CRISPR genome editing has revolutionized our ability to treat genetic disorders and cancer at their root cause. While significant technical and ethical challenges remain, ongoing advances in delivery, editing precision, and clinical trial design continue to bring this technology closer to widespread clinical use. With responsible development and global oversight, CRISPR holds transformative potential for 21st-century medicine.CRISPR genome editing has revolutionized our ability to treat genetic disorders and cancer at their root cause. While significant technical and ethical challenges remain, ongoing advances in delivery, editing precision, and clinical trial design continue to bring this technology closer to widespread clinical use. With responsible development and global oversight, CRISPR holds transformative potential for 21st-century medicine.
- Keywords: CRISPR, cancer
