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Allele-specific genome targeting in the development of precision medicine

The CRISPR-based genome editing holds immense potential to fix disease-causing mutations, however, must also handle substantial natural genetic variations between individuals. Previous studies have shown that mismatches between the single guide RNA (sgRNA) and genomic DNA may negatively impact sgRNA...

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Autores principales: Wu, Junjiao, Tang, Beisha, Tang, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053192/
https://www.ncbi.nlm.nih.gov/pubmed/32194858
http://dx.doi.org/10.7150/thno.43298
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author Wu, Junjiao
Tang, Beisha
Tang, Yu
author_facet Wu, Junjiao
Tang, Beisha
Tang, Yu
author_sort Wu, Junjiao
collection PubMed
description The CRISPR-based genome editing holds immense potential to fix disease-causing mutations, however, must also handle substantial natural genetic variations between individuals. Previous studies have shown that mismatches between the single guide RNA (sgRNA) and genomic DNA may negatively impact sgRNA efficiencies and lead to imprecise specificity prediction. Hence, the genetic variations bring about a great challenge for designing platinum sgRNAs in large human populations. However, they also provide a promising entry for designing allele-specific sgRNAs for the treatment of each individual. The CRISPR system is rather specific, with the potential ability to discriminate between similar alleles, even based on a single nucleotide difference. Genetic variants contribute to the discrimination capabilities, once they generate a novel protospacer adjacent motif (PAM) site or locate in the seed region near an available PAM. Therefore, it can be leveraged to establish allele-specific targeting in numerous dominant human disorders, by selectively ablating the deleterious alleles. So far, allele-specific CRISPR has been increasingly implemented not only in treating dominantly inherited diseases, but also in research areas such as genome imprinting, haploinsufficiency, spatiotemporal loci imaging and immunocompatible manipulations. In this review, we will describe the working principles of allele-specific genome manipulations by virtue of expanding engineering tools of CRISPR. And then we will review new advances in the versatile applications of allele-specific CRISPR targeting in treating human genetic diseases, as well as in a series of other interesting research areas. Lastly, we will discuss their potential therapeutic utilities and considerations in the era of precision medicine.
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spelling pubmed-70531922020-03-19 Allele-specific genome targeting in the development of precision medicine Wu, Junjiao Tang, Beisha Tang, Yu Theranostics Review The CRISPR-based genome editing holds immense potential to fix disease-causing mutations, however, must also handle substantial natural genetic variations between individuals. Previous studies have shown that mismatches between the single guide RNA (sgRNA) and genomic DNA may negatively impact sgRNA efficiencies and lead to imprecise specificity prediction. Hence, the genetic variations bring about a great challenge for designing platinum sgRNAs in large human populations. However, they also provide a promising entry for designing allele-specific sgRNAs for the treatment of each individual. The CRISPR system is rather specific, with the potential ability to discriminate between similar alleles, even based on a single nucleotide difference. Genetic variants contribute to the discrimination capabilities, once they generate a novel protospacer adjacent motif (PAM) site or locate in the seed region near an available PAM. Therefore, it can be leveraged to establish allele-specific targeting in numerous dominant human disorders, by selectively ablating the deleterious alleles. So far, allele-specific CRISPR has been increasingly implemented not only in treating dominantly inherited diseases, but also in research areas such as genome imprinting, haploinsufficiency, spatiotemporal loci imaging and immunocompatible manipulations. In this review, we will describe the working principles of allele-specific genome manipulations by virtue of expanding engineering tools of CRISPR. And then we will review new advances in the versatile applications of allele-specific CRISPR targeting in treating human genetic diseases, as well as in a series of other interesting research areas. Lastly, we will discuss their potential therapeutic utilities and considerations in the era of precision medicine. Ivyspring International Publisher 2020-02-10 /pmc/articles/PMC7053192/ /pubmed/32194858 http://dx.doi.org/10.7150/thno.43298 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Review
Wu, Junjiao
Tang, Beisha
Tang, Yu
Allele-specific genome targeting in the development of precision medicine
title Allele-specific genome targeting in the development of precision medicine
title_full Allele-specific genome targeting in the development of precision medicine
title_fullStr Allele-specific genome targeting in the development of precision medicine
title_full_unstemmed Allele-specific genome targeting in the development of precision medicine
title_short Allele-specific genome targeting in the development of precision medicine
title_sort allele-specific genome targeting in the development of precision medicine
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7053192/
https://www.ncbi.nlm.nih.gov/pubmed/32194858
http://dx.doi.org/10.7150/thno.43298
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