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Clinical Genetics and Genomics of Aging pp 213–230Cite as

Applications of CRISPR-Cas in Ageing Research

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Abstract

Genetic and genomic manipulation lie as the cornerstones of several important discoveries in biomedical science. For more than four decades, scientists have targeted genes and their function using molecular biology techniques in various organisms and cells, ranging from the simplest of bacteria to primates and even humans. In the last years, CRISPR-Cas technology has demonstrated to be a fast, efficient and precise method for modifying from a single nucleotide in a cell’s DNA to whole genomes. Moreover, the flexibility of this technique has allowed researchers to develop newer and improved CRISPR-based solutions to some of the most challenging questions in genetics. As many biological processes, ageing is affected by complex interactions between several genetic and epigenetic mechanisms, posing great challenges to scientists attempting to understand this phenomenon and its causes or aiming to develop treatments for age-related diseases. CRISPR-Cas showed to be a promising tool for the manipulation of gene function and regulation in traditional models of ageing, shedding light into the roles of telomeric attrition, epigenetic dysregulation and cellular senescence. Additionally, it has greatly accelerated the efficient development of novel animal and cell models for the study of those processes and ageing-related pathologies.

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Abbreviations

AAV:

Adeno-associated virus

AD:

Alzheimer’s disease

Cas9:

CRISPR-associated protein 9

CRISPR:

Clustered regularly interspaced short palindromic repeat

CRISPRi:

CRISPR interference

dCas9:

Nuclease-deficient Cas9

DSB:

Double-strand break

ES:

Embryonic stem

gRNA:

Guide RNA

HDR:

Homology-directed repair

HGPS:

Hutchinson-Gilford progeria syndrome

iPSC:

Induced pluripotent stem cell

Lmna :

Lamin A gene

lncRNA:

Long non-coding RNA

miRNA:

MicroRNA

ncRNA:

Non-coding RNA

PAM:

Protospacer adjacent motif

PD:

Parkinson’s disease

SASP:

Senescence-associated secretory phenotype

TALEN:

Transcription activator-like effector nuclease

TERT:

Telomerase reverse transcriptase

ZNF:

Zinc finger nuclease

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Acknowledgements

JMGM is part of the Translational OMICS Strategic Focus Group at Tecnologico de Monterrey.

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Authors and Affiliations

  1. Developmental Biology and Cancer Research Programme, Birth Defects Research Centre, UCL Great Ormond Street Institute of Child Health, London, UK

    Scott Haston

  2. The Novo Nordisk Foundation Center for Stem Cell Biology, University of Copenhagen, Copenhagen, Denmark

    Sara Pozzi

  3. Bioengineering Department, School of Engineering and Science, Tecnologico de Monterrey, Mexico City, Mexico

    Jose Mario Gonzalez-Meljem

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  1. Scott Haston
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  2. Sara Pozzi
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Correspondence to Jose Mario Gonzalez-Meljem .

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Editors and Affiliations

  1. Basic Sciencies Division, National Institute of Geriatrics, Ciudad de México, Mexico

    Juan Carlos Gomez-Verjan

  2. Instituto Nacional de Geriatría (INGER), Ciudad de México, Mexico

    Nadia Alejandra Rivero-Segura

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Haston, S., Pozzi, S., Gonzalez-Meljem, J.M. (2020). Applications of CRISPR-Cas in Ageing Research. In: Gomez-Verjan, J., Rivero-Segura, N. (eds) Clinical Genetics and Genomics of Aging. Springer, Cham. https://doi.org/10.1007/978-3-030-40955-5_11

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