Sciences de la Santé
Review : CRISPR-CAS9 , Genetic Editing Technology
Yahia BELLOUCHE M . D .
Abstract The explosive development in the domains of microscopy , data analysis and molecular biology
have led us to a better understanding of cell functioning . Basic the sequence gene-protein- function might be , further mapping of the different loci and their products allowed a larger view on the pathophysiology of many illnesses , that said , almost every pathological process we could meet in the different entities , contain a quantitative and / or qualitative disorder in the sequence above . All that opened the debate on the importance of the genome and the potential benefits of the technologies of genetic editing such as the CRISPR-CAS9 system , subject of our discussion .
Basic concepts
Every Cell in the body holds a complete copy of the genome , which is a set of DNA chains , organized in different structural levels , resulting from chemical links between millions of nucleic acids . Each gene occupies a definite place called a locus that codes for at least one “ functional molecule ”, proteins mostly , that induce a given change somewhere in the cell or out of intracellular compartment . The sequence explained above is not in fact simple , many processes follow up to the final effector . Copies are made of the gene in the form of mRNA after transcription , they transit into the cytosol and get translated by means of polysomes onto proteins that can submit some modification ( glycosylation , cleavage , conformational maturity ….), before they get addressed to the corresponding compartment where they accomplish the tasks supposed . This model implies an “ On demand ” gene expression system rather than a “ Continuous ” one . The general regulation loop scheme is very much valid In this context , this means that a stimulus can induce which gene to be expressed and when , recent data suggests further control of external milieu , one that commands how and what is transcribed in a gene , which means that a phenotype is in fact , an interaction product between an intrinsic genetic code and some surrounding conditions , study subject for Epigenetics . As a result , the environment of a cell and its level of differentiation define various functional stages where a cell performs different tasks and exposes many changes . The pool of proteins expressed by a cell in a given functional state is known as a proteome , its field of study Proteomics . Same definitions can be applied to the genome , genomics respectively . Considering now the pathological side , an interactive and dynamic genome , beneficial for a cell on one
hand , would only mean extra vulnerability to modifications and alterations on the other . A fact that can be largely deduced from the genetic analysis of affected cells from many examples such as cancer , viral infections and inflammatory response . However , those are extremely rare , and even with the presence of many potential alteration inducers , the genome is somewhat sane , this has been studied largely through the last decade and many protection systems were discovered , the CRISPR-CAS9 being one of those .
CRISPR-CAS9 system in prokaryotes Experimental data from the 1980s discovered that species of E . Coli could resist a viral infection after a few generations , raising a question about the mechanisms . Bacteriophages ( viruses infecting bacteria ) contain some genetic sequences that – after penetration- get integrated in the bacteria genome causing alterations and modifications through transcription . These sequences code for viral structure proteins and mandatory enzymatic material . Throughout the natural history of infection , some colonies begin to expose a certain degree of resistance , documented by the deceleration of viral multiplication rates . Further analysis of the bacterial genome detected some DNA sequences originating from the virus itself . The questions about the mechanisms were not solved until 2007 with the work of Barrangou & Col , where the CRISPR-CAS system was well understood . Studies have concluded that some gene loci in the genome were the association result of pieces of repetitive sequences and some viral sequences called spacers . That said , the CRISPR loci transcription product was found to be a special type of RNA ( called crRNA ) that had the ability to bind a set of proteins such as CAS , the resistance to viral infection appears after two phases ,
12 Hiver 2018