Restoring the p53 'Guardian' Phenotype in p53-Deficient Tumor Cells with CRISPR/Cas9

Sergiu Chira1, Diana Gulei2, Amin Hajitou3

  • 1Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania.

Trends in Biotechnology
|February 27, 2018
PubMed

Insights

This study introduces a novel CRISPR/Cas9 system to restore the tumor suppressor gene TP53 in cancer cells. The approach aims to replace mutant TP53 with a functional copy, potentially leading to tumor regression.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Cancer is a prevalent disease with TP53 mutations found in ~50% of human cancers.
  • Mutated TP53 is often linked to a poor prognosis in cancer patients.
  • Targeting tumor suppressor genes is a key area in cancer therapy research.

Purpose of the Study:

  • To develop a novel, tumor-specific delivery system for the TP53 gene.
  • To restore the normal p53 phenotype in cancer cells using genome editing.
  • To investigate the potential of this system for inducing tumor regression.

Main Methods:

  • Utilizing CRISPR/Cas9 genome editing technology for gene replacement.
  • Designing a system for highly tumor-specific delivery of the functional TP53 gene.
  • Focusing on restoring wild-type TP53 expression in malignant cells.

Main Results:

  • The proposed system aims to replace mutant TP53 with a functional copy in tumor cells.
  • Successful restoration is expected to lead to sustained p53 protein expression.
  • The ultimate goal is to achieve tumor regression through this gene-editing approach.

Conclusions:

  • A novel CRISPR/Cas9-based system offers a targeted approach for TP53 restoration in cancer.
  • This strategy holds promise for treating cancers with TP53 mutations.
  • Restoring p53 function could be a viable therapeutic avenue for cancer treatment.

Related Concept Videos

CRISPR01:59

CRISPR

Genome editing technologies allow scientists to modify an organism’s DNA via the addition, removal, or rearrangement of genetic material at specific genomic locations. These types of techniques could potentially be used to cure genetic disorders such as hemophilia and sickle cell anemia. One popular and widely used DNA-editing research tool that could lead to safe and effective cures for genetic disorders is the CRISPR-Cas9 system. CRISPR-Cas9 stands for Clustered Regularly Interspaced...
46.4K
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
8.5K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.0K
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
2.4K
CRISPR/Cas9 Genome Editing01:28

CRISPR/Cas9 Genome Editing

The CRISPR-Cas system serves as a bacterial defense mechanism against invading genetic elements such as viruses and plasmids, forming the foundation for its adaptation as a powerful genome-editing tool. Originally discovered in prokaryotes, this system has been repurposed to revolutionize genetic engineering across a wide range of organisms, including plants, animals, and humans. The core component, Cas9, is an endonuclease derived from Streptococcus pyogenes, capable of introducing...
3.2K