Complex human diseases such as cancer can arise from defects in multiple molecular pathways. Despite the need for new combination therapies that simultaneously target multiple disrupted gene networks, previous techniques for discovering disease-related gene combinations have been expensive, labor-intensive, and challenging to scale.
Researchers developed a simple, efficient screening platform to identify gene pairs that act synergistically to regulate disease-related cellular processes. The authors used a recently developed approach called combinatorial genetics en masse (CombiGEM) to rapidly create a library of 23,409 pairwise combinations of guide-RNAs (gRNAs).
The gRNA molecules form a complex with the Cas9 enzyme to generate mutations at specific genomic sites. Leveraging this genome-editing approach, known as the CRISPR-Cas9 system, the authors delivered gRNA pairs into human ovarian cancer cells, thereby simultaneously generating mutations in gene pairs.
The CombiGEM-CRISPR screening platform revealed several gene pairs that acted synergistically to regulate cancer cell growth. For example, gRNA pairs that simultaneously targeted the KDM4C and BRD4 genes reduced cancer cell growth to a greater extent than individual gRNAs that targeted only one of these genes.
According to the authors, the CombiGEM-CRISPR platform could facilitate the discovery of synergistic drug combinations for complex human diseases.
http://www.pnas.org/content/early/2016/02/09/1517883113
Screening platform for drug discovery
- 1,621 views
- Added
Edited
Latest News
Which of the two DNA strand…
By newseditor
Posted 16 Jun
Microglia depletion prevent…
By newseditor
Posted 16 Jun
Colorectal cancer stem cell…
By newseditor
Posted 16 Jun
Paranoia in the brain
By newseditor
Posted 16 Jun
In-vitro 3D culture of func…
By newseditor
Posted 15 Jun
Other Top Stories
Origin of neural crest cells identified!
Read more
Lymphatic system found to play key role in hair regeneration
Read more
Transient wave of hematopoietic stem cell production in late fetuse…
Read more
Plectin protein as a potential biomarker for lung cancer stem cells
Read more
How bone marrow stem cells get energy to fight infection
Read more
Protocols
Bioengineered human colon o…
By newseditor
Posted 14 Jun
Development of an efficient…
By newseditor
Posted 12 Jun
A co-culture system of macr…
By newseditor
Posted 10 Jun
Analysis of 3D pathology sa…
By newseditor
Posted 08 Jun
Long-term expandable mouse…
By newseditor
Posted 07 Jun
Publications
Pathways for macrophage upt…
By newseditor
Posted 16 Jun
Common and distinct neural…
By newseditor
Posted 16 Jun
Strand-resolved mutagenicit…
By newseditor
Posted 16 Jun
Innate-like T cells in live…
By newseditor
Posted 16 Jun
Membrane to cortex attachme…
By newseditor
Posted 16 Jun
Presentations
Myelin plasticity in the ve…
By newseditor
Posted 10 Jun
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar