CRISPR gene editing tool was used to identify synthetic-lethal genetic interactions which could be used to develop new drug targets for cancer therapy.
Highlights:
A
research team from UC San Diego School
of Medicine and Jacobs School of
Engineering has identified a novel method of finding mutated (synthetic)
cells. These ‘synthetic cells’ are cells that have undergone genetic mutations
and which have developed into cancers; however, the mutations also tend to
weaken the cells. This is called ‘synthetic lethality’ and this concept
can be used for drug therapy. The results of the study were published in Nature Methods, with over 120 new
strategies for cancer drug development.
A
clinical instructor and postdoctoral fellow at UC San Diego School of Medicine
and Moores Cancer Center, Dr. John Paul Shen said that the drug Olaparib, given
for ovarian cancer, works on the basis of synthetic lethality. This drug blocks
a gene which leads to the death of BRCA
mutated cancer cells. Dr. Shen, who is the co-first author of the study,
further stated that many cancers could be treated using this method but there
is currently no comprehensive list of the gene combinations that are
synthetic-lethal. - A research team, from Jacob’s School of Engineering, used the genome editing tool CRISPR to identify gene interactions in synthetic or mutated cancer cells
- The scientists identified 120 novel synthetic-lethal gene combinations
- Synthetic lethality is a method for drug therapy whereby potential new drugs can be designed
The Breakthrough of 2015 - CRISPR
CRISPR is a gene editing tool that is revolutionizing medical care with prospective cure for genetic diseases like cancer, diabetes, DMD, eye diseases, obesity.
CRISPR is a gene editing tool that is revolutionizing medical care with prospective cure for genetic diseases like cancer, diabetes, DMD, eye diseases, obesity.
‘CRISPR can be used effectively to identify synthetic-lethal gene mutation combinations in cancer cells to help develop drugs against the disease.’
CRISPR/Cas9 System
The process of identifying gene combinations that are lethal can be laborious; however, this process is reduced by using the gene editing tool CRISPR/Cas9. This popular tool can test for thousands of synthetic-lethal combinations at the same time.Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated system or Cas genes are required for adaptive immunity among certain bacterial species, which allows these organisms to react to the invading genetic material. The gene editing tools were discovered in E. coli in 1980 but their function did not become evident till 2007. It was shown that S. thermophilus could develop a resistance towards infection by a bacteriophage by integrating a fragment of the genome of the infectious agent into its locus.
Types of CRISPR
There are three different types of CRISPR which have been identified among which type 2 is well known. In the type 2 form of CRIPSR- The DNA from the invading plasmids or viruses are cut into smaller fragments
- These fragments are then incorporated into the CRISPR locus in between short repeats
- There is transcription of the loci; the transcripts are then processed to result in small RNAs
- These small RNAs guide the endonucleases which target the DNA of the invading virus or plasmid based on complementarity
- The Cas9 protein is required for gene silencing
- The protein is also required for the synthesis of CRISPR RNA as well as for the destruction of the target DNA
- Targeting the commonly mutated tumor suppressing gene
- Targeting a gene that can be disrupted by a drug for cancer
Crispr Cas9 Effective against Genetic Disorder
Scientists have altered hematopoietic stem cells from patients with chronic granulomatous disease using CRISPR-Cas9 and successfully injected into the host.
Scientists have altered hematopoietic stem cells from patients with chronic granulomatous disease using CRISPR-Cas9 and successfully injected into the host.
Synthetic-lethal Interactions
The synthetic-lethal interactions that were identified were found in just one of the three cell lines that were tested, indicating that the interactions were different for the different types of cancer. This is a critical understanding for drug development.Advertisement
Crispr Screening Successfully Identifies Potential HIV Treatment Targets
CRISPR genome screening identifies human ‘host’ genes that promote HIV infection, which might be targeted in HIV treatment in the future.
CRISPR genome screening identifies human ‘host’ genes that promote HIV infection, which might be targeted in HIV treatment in the future.
CRISPR in Cancer Research
Dr. Si Chen and colleagues published a paper in the International Journal of Biological Sciences titled “CRISPR-Cas9: from Genome Editing to Cancer Research”. The development of cancer involves multiple steps and is associated with innate mutations as well as mutations that are acquired. These mutations lead to the functional abnormality seen in cancer and they determine the progress of cancer. The CRISPR-associated 9 (CRISPR-Cas9) system provides a genome editing approach which is convenient.Advertisement
First Human Trial of Crispr Cas9 System Raises Hope for Cancer Cure
The first ever human trial of CRISPR-Cas9 system was successfully conducted on a lung cancer patient who did not respond to chemotherapy and radiation.
The first ever human trial of CRISPR-Cas9 system was successfully conducted on a lung cancer patient who did not respond to chemotherapy and radiation.
- Loss of function of gene-screening invivo
- Gain of function of gene-screening invivo
- Acceleration of cancer in animal models for research purposes
- Potential use in gene therapy for cancer
References:
- CRISPR-Cas9: from Genome Editing to Cancer Research - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5166485/)
