Related Experiment Video
Updated: Jun 10, 2026
07:23
Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells
Published on: May 30, 2025
Targeting cancer-specific mutations with RNA-triggered chromatin shredding
Jingkun Zeng1,2,3,4, Zhiyuan Cheng1,2,5, Huadong Chen6
1Gladstone Institute of Data Science and Biotechnology, San Francisco, CA, USA.
Nature
|June 8, 2026
Summary
Researchers developed a new CRISPR-Cas12a2 system to target cancer-specific RNA, leading to chromatin shredding and cancer cell death. This approach offers a novel strategy for treating cancers with undruggable mutations.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Genetic mutations in tumor suppressor proteins like p53 are common drivers of cancer.
- Current therapies struggle to target these mutations due to a lack of drug-binding pockets and challenges in restoring protein function.
Purpose of the Study:
- To develop a novel therapeutic strategy for targeting cancer-specific transcripts.
- To utilize CRISPR-Cas12a2 for selective cancer cell killing via RNA-guided chromatin shredding.
Main Methods:
- Programmed CRISPR-Cas12a2, an RNA-guided nuclease, to target cancer-specific transcripts.
- Induced trans-nucleolytic cleavage of target RNA, leading to chromatin shredding.
- Triggered DNA damage responses and cell death in cancer cells.
Main Results:
- Demonstrated selective killing of cancer cells by targeting cancer-specific RNA signatures.
- Showcased transcript-activated chromatin shredding as a mechanism for cancer cell death.
- Validated the potential of RNA-guided Cas12a2 for targeting previously undruggable mutations.
Conclusions:
- CRISPR-Cas12a2 offers a precise method for targeting cancer-specific transcripts.
- Transcript-activated chromatin shredding presents a new therapeutic avenue for cancers with undruggable targets.
- This approach enhances precision medicine by addressing genetic mutations resistant to conventional therapies.
More Related Videos
Related Concept Videos
02:57Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...
02:57Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...
02:15Experimental RNAi
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
02:50Combination Therapies and Personalized Medicine
Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:56Treatment Resistant Cancers
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
02:53Conservative Site-specific Recombination and Phase Variation
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...