Different research groups, using the CRISPR-cas system of the bacteria Streptococcus pyogenes, engineered a version of an RNA molecule, named guide RNA (gRNA)[19, 20]. Once again, we would emphasize the importance of ensuring the safety and precision of CRISPR-cas9 systems in gene-editing, before considering clinical trials. Data Availability: The search terms used to generate the data underlying this study are included in S1 Table. Read more. Lee et al. Fig 3 depicts the number of publications per year and disease type. (2017) [39] and Bengtsson et al. An elongated transcribed mRNA shows toxic effects in the cells due to mis-splicing of proteins, which leads to myotonia, muscular wasting (see a schematic depiction of a typical phenotype in a boy with congenital DM1), and endocrine disorders. The discovery of CRISPR-cas split the public opinion. Disease progression leads to upper-limb and distal muscle weakness. [127], Most of the NMGDs have a low prevalence in the overall population. The development of a CRISPR-cas treatment already raises some complex ethical concerns that need to be addressed and considered when designing both preclinical and clinical studies. Yet it may surprise you to find out that CRISPR itself is not a machine, a computer program or even a human invention—it’s actually an ancient, naturally occurring defence system. Dr. Jeniffer Doudna, one of the pioneers of CRISPR-cas9, has asked for moratorium on human embryonic stem cells genome editing on several occasions. Furthermore, it would increase the costs of the treatment. The two seem to show no differences in editing efficacy. Found in a range of bacteria, CRISPR defends cells by identifying the DNA of invading viruses and, together with a protein made by the bacteria, slicing parts out of the virus to deactivate it—like a pair of DNA-cutting scissors. [79], Delivery still remains a major bottleneck. However, the treated muscle tissues had higher numbers of CD45+ CD11b+ cells compared to controls. [84, 85] Probability of survival after the age of 65 years is low. All of them have their own advantages and disadvantages, discussed in detail by Liu et al. Johnathan Edwards. The authors report that this is likely attributable to the presence of two FXN transgenes in tandem in the genome of YG8R mice, leading to a deletion of not only the repeats, but of one entire copy. Cas is the ‘cutting’ part of the defence mechanism, and scientists have found that the genes that encode for Cas are always somewhere near the CRISPR sequences. [27] BMD has lower prevalence (1 in 11,500 men), later onset and a varying presentation. You may know that it’s got something to do with editing genes, that it was recently used for the first time to genetically alter a human embryo, and that it’s generating a lot of discussion. The aim of this systematic review was to summarise the findings on the current development of CRISPR-cas for therapeutic purposes in the most frequent NMGDs and provide critical assessment. The study shows the CRISPR-edited parasites do not cause disease in animal models of sand flies, which spread the parasite through their bite, and mice. A homozygous mutation in the FXN gene leads to epigenetic deregulation and reduced expression of the frataxin protein to levels 5–35% of those of healthy individuals. This led to the adaptation of the CRISPR-cas systems for genome editing (Fig 1). But they persist in the body for eight or nine months, which is long enough to generate acquired immunity.”. This dCas9 can still bind to the sgRNA and thereby be directed to different loci in the genome. They report little or no off-target editing in the predicted off-target loci, as observed with the T7E1 assay. The researchers are now looking to begin Phase 1 human trials within the next two years. It usually manifests with waddling gait, skeletal and respiratory muscle weakness, and cardiomyopathy. Funding: The author(s) received no specific funding for this work. Frataxin is involved in the function of mitochondria. Potential unwanted or unwarranted changes in the genome would be additionally passed on to children who are not in a position to give an informed consent. [27] In the past, DMD patients were dying usually in their teenage and adolescent years. (2017) brings excitement in the research community due to several reasons. These are individually taken up by Cas proteins, together with another kind of RNA, known as trans-activating RNA. These are usually clustered at “hotspot” regions: between exons 2–20 and exons 44–53. [57, 76] Although promising, the efficacy of HC-Adv delivery is yet to be confirmed in vivo. According to the definition of a rare disease as such of “a prevalence of not more than five affected persons per ten thousand”, all the diseases that we have discussed in this review are rare diseases. None of these genome-editing tools have sparked such interest in the scientific community as did the discovery of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated protein (cas) systems[10].