Cutting Edge CRISPR Cas9 Applications

In 2015, the journal Science chose CRISPR-Cas9 technology as one of the most important technological advances in science in the last few years.

Gene editing is the new era of biotechnology, which makes it possible to edit, correct and modify the genetic information of any cell in a precise, fast and cheap way. CRISPR-Cas and genome engineering research fields are two fields which merged in 2012 with the discovery that Cas9 is an RNA-programmable DNA endonuclease, leading to many scientific papers beginning in 2013 in which Cas9 has been used to modify genes in human cells as well as many other cell types and organisms [1].

The genome-editing system based on CRISPR-Cas is becoming a valuable tool for different applications in biomedical research, drug discovery and human gene therapy by gene repair and gene disruption, gene disruption of viral sequences, and programmable RNA targeting [1,2].

Genome editing is the most efficient technique in terms of manipulating the gene expression by using programmable DNA nuclease comparing to gene transfer approaches. Nowadays, the four genome-editing platforms mostly used are: meganucleases, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the CRISPR–Cas system [1,3-5]. Currently, it is possible to correct many genetic diseases with genome-editing technologies but there are some obstacles and challenges to overcome such as the genome-editing biomacromolecules. Hao Yin et al., has given a very interesting overview about the different programmable nucleases and mechanisms of genome editing, by focusing on the principles of biomacromolecules delivery, relevant delivery methods and associated delivery challenges. 

Furthermore, cancer is one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases in 2012 [6]. I strongly believe in the importance of exploring innovative approaches to study cancer on the genomic, epigenetic and transcriptional level at highest-possible resolution.

Nowadays, many diseases such as cancer have risen to the forefront of genomic profiling, which are being used to identify actionable driver mutations and other markers. These investigations can help clinicians design therapies and monitor patient responses. In addition, new technologies are being established such as induced pluripotent stem cells (iPS) models that are very well established, can be used for regenerative medicine. In addition to the iPS cells, one of the revolutionary genetic tools is the CRISPR technique that facilitates the genomics studies in all model organisms. Scientists are engineering the CRISPR-Cas9 into a screening tool, they can modify sites by knockout at a genome-wide scale, or they use other options including loss-of-function or gain-of-function screens that use transcriptional activation (CRISPRa), transcriptional repression (CRISPRi), base editing, directed mutagenesis, epigenetic editing, RNA interference (RNAi) or combinatorial methods. MIT–Harvard team has built Combi-GEM-CRISPR for high-throughput combinations of genetic perturbations to explore, in parallel, how different gene networks or epigenetic regulators shape cancer cell phenotypes [7]. Generally speaking, pharmaceutical researchers screen in cell lines, but comprehensive genetic validation after that step has been challenging said Dr Johannes Zuber, a researcher at The Research Institute of Molecular Pathology in Vienna. New tools are changing this, which might alter the approximately 90% failure rate of cancer drug candidates. With CRISPR- and RNAi-based techniques labs might more readily identify and validate new candidate targets in much greater depth, he says, and generate animal models that better reflect the genetic complexity of human tumors.

Let’s go further with the use of genome editing technique for cellular improvements. Dr Marc Tessier-Lavigne, a neuroscientist at the Rockefeller University in 

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