Novel gene editing technique reveals cancer weakness in the immune system and opens possibilities to identify disease-causing genes and new drug targets
Scientists at Mount Sinai have developed a novel technology for simultaneously analyzing the functions of hundreds of genes with resolution reaching the single cell level. The technology relies on a barcoding approach using a novel protein described in a paper published in the journal Cell.
Since the sequencing of the first human genome in the early 2000s revealed a set of more than 20,000 protein-coding genes, scientists have not yet been able to characterize the many functions of individual gene. Without that information, our understanding of how the human genome works — and how to use that knowledge to predict, prevent, treat and even cure disease — is limited. In 2012 and 2013, scientists established a powerful new approach for editing genes, called CRISPR, which can be used to determine gene functions. CRISPR has taken the scientific world by storm, but researchers have still been challenged with using CRISPR to study the many thousands of genes and their numerous possible roles.
A new technology developed by scientists at the Icahn School of Medicine at Mount Sinai helps address the genomics challenge of analyzing the genome at an unprecedented scale. The research, led by postdoctoral fellows Aleksandra Wroblewska, PhD and Maxime Dhainaut, PhD, is novel tool to barcode and track different CRISPRs using synthetic proteins called epitopes. The protein barcodes referred to as Pro-codes, enables hundreds of CRISPRs to be used together to knockout a multitude of genes.
While there are existing technologies for pooling CRISPRs, these approaches rely heavily on DNA as a barcode and permit only a low resolution look into gene function. Through the Pro-Code technique, Mount Sinai researchers were able to demonstrate a way for scientists to more comprehensively characterize the biological effects of a gene.,
In the study, the researchers used the Pro-Code technology to search for genes required for the immune system to protect from cancer. They generated CRISPRs to target the deletion of suspected immune regulatory genes, and paired them with the Pro-Codes. Pro-Code/CRISPR libraries were then introduced to breast cancer cells, and the tumors were challenged with killer T cells that had been engineered to recognize the cancer cells. Most of the cancer cells were rapidly eliminated by the T cells but there were some cells that completed resisted death. The Pro-Code technology helped determine which genes were lost in the resistant cells some with unrecognized roles in sensitizing cancer cells in the immune system. The studies also identified a negative regulator of the immune checkpoint PD-L1, a major clinical target of cancer immunotherapy.
“There is still a great deal of work to be done to fully understand the human genome. We still don’t know what most genes do and how they are connected,” said Brian Brown, PhD, Associate Professor of Genetics and Genomic Sciences and Associate Director of the Immunology Institute at the Icahn Institute at Mount Sinai and senior author of the publication. “The Pro-Code technology could greatly accelerate one of the major goals of the post-genome era: annotation of the human genome. This discovery will be key to discover disease-causing genes that could lead to novel drug targets. It’s already given us new insights in cancer immunology.”
Receive an email update when we add a new GENETIC BARCODING article.
The Latest on: Genetic barcoding
via Google News
The Latest on: Genetic barcoding
- Sequencing pollen DNA to discover insect migratory routes on November 12, 2018 at 6:57 am
A small DNA fragment of the pollen that insects transport is used as a barcode to identify the plant ... made it possible to massively sequence the genetic material present in a sample of pollen ... […]
- Method spotlights best nanoparticles to deliver genetic drugs on October 31, 2018 at 12:10 pm
Genetic sequencing techniques then identify which DNA-labeled ... that the nanoparticles have entered the cells of the specific organs. In addition to the DNA barcode, the researchers inserted into ea... […]
- Critical cancer immunity genes identified using new genetic barcoding technology on October 21, 2018 at 8:23 am
Scientists have developed a novel way to barcode and track different CRISPRs by utilizing synthetic proteins built from combinations of smaller proteins, called epitopes. By being able to mark each CR... […]
- Scientists identify critical cancer immunity genes using new genetic barcoding technology on October 19, 2018 at 11:30 pm
Scientists at Mount Sinai have developed a novel technology for simultaneously analyzing the functions of hundreds of genes with resolution reaching the single cell level. The technology relies on a b... […]
- LIMS Made Freely Available to DNA Barcoding Community on September 13, 2018 at 5:00 pm
In addition to tracking down all the biodiversity in this tropical island ecosystem, one of the promised deliverables has been an informatics tool to allow easy access to those data and to aid other g... […]
- Developmental barcoding of whole mouse via homing CRISPR on August 30, 2018 at 5:00 pm
A homing guide RNA (hgRNA) that directs CRISPR-Cas9 to its own DNA locus can diversify its sequence and act as an expressed genetic barcode. Kalhor et al. engineered a mouse line carrying 60 independe... […]
- New way to understand tumor diversity combines CRISPR with genetic barcodes on April 10, 2018 at 1:37 pm
Stanford researchers develop a new way to track the growth of diverse tumor types, using gene editing and DNA barcoding. The growth of a particular tumor depends on multiple genetic factors, so it's d... […]
- Scientists combine CRISPR, DNA barcoding to track cancer growth on April 4, 2018 at 9:25 am
Each sequence functions as a heritable genetic barcode, and as each cancer seed cell divides, growing into a tumor, the number of barcodes also multiplies. Now, instead of having to painstakingly cut ... […]
- Stanford scientists combine CRISPR and DNA barcoding to track cancer growth on April 4, 2018 at 7:43 am
Stanford researchers say the combination of CRISPR-Cas9 and DNA barcoding could allow scientists to replicate in the lab the kind of genetic diversity observed in cancer patients. (Image credit: Court... […]
via Bing News