common mutation causing CF in intestinal organoids They demonstrated that once

Common mutation causing cf in intestinal organoids

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commonmutationcausing CF in intestinal organoids. Theydemonstrated that once the mutation hadbeen corrected, the function of the CFtransmembraneconductorreceptor(CFTR) was restored.4Another disease in which CRISPR/Cas9has been investigated is DMD. Tabebordbaret alrecently used adeno-associated virus(AAV) delivery of CRISPR/Cas9 endonu-cleases to recover dystrophin expression ina mouse model of DMD, by deletion of theexon containing the original mutation. Thisproduces a truncated, but still functionalprotein. Treated mice were shown to par-tially recover muscle functional deficien-cies.5Significantly, it was demonstrated thatthe dystrophin gene was edited in musclestem cells which replenish mature muscletissue. This is important to ensure anytherapeutic effects of CRISPR/Cas9 do notfade over time. Two similar studies havedescribed using the CRISPR/Cas9 system invivo to increase expression of the dys-trophin gene and improve muscle functionin mouse models of DMD.6 7Other studieshave used CRISPR/Cas9 to target duplica-tion of exons in the human dystrophin genein vitro and have shown that this approachcan lead to production of full-length dys-trophin in the myotubules of an individualwith DMD.8CRISPR/Cas9couldalsobeusedtotreat haemoglobinopathies. Canveret al9recently showedBCL11Aenhancer dis-ruptionbyCRISPR/Cas9could inducefetalhaemoglobininbothmiceandprimary human erythroblast cells. In thefuture such an approach could allow fetalhaemoglobin to be expressed in patientswith abnormal adult haemoglobin. Thiswould represent a novel therapeutic strat-egyinpatientswithdiseasessuchassicklecelldiseaseorthalassaemias.RESEARCH IN PRACTICERedman M,et al.Arch Dis Child Educ Pract Ed2016;0:1 3. doi:10.1136/archdischild-2016-310459 1 Education & Practice Online First, published on April 8, 2016 as 10.1136/archdischild-2016-310459 Copyright Article author (or their employer) 2016. Produced by BMJ Publishing Group Ltd under licence. group.bmj.com on April 16, 2016 - Published by Downloaded from
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Knock-in of a fully functional β -globin gene is much more challenging, which is the reason for this some- what unusual approach. Treatment of HIV Another potential clinical application of CRISPR/Cas9 is to treat infectious diseases, such as HIV. Although antiretroviral therapy provides an effective treatment for HIV, no cure currently exists due to permanent integration of the virus into the host genome. Hu et al showed the CRISPR/Cas9 system could be used to target HIV-1 genome activity. This inactivated HIV gene expression and replication in a variety of cells which can be latently infected with HIV, without any toxic effects. Furthermore, cells could also be immu- nised against HIV-1 infection. This is a potential thera- peutic advance in overcoming the current problem of how to eliminate HIV from infected individuals. After further refinement, the authors suggest their findings may enable gene therapies or transplantation of genet-
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