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Genetic advancements in obesity management and CRISPR–Cas9-based gene editing system

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Abstract

Human genome research has reached new heights in the recent decade thanks to a major advance in genome editing. Genome editing enables scientists to understand better the functions of a single gene and its impact on a wide range of diseases. In brief, genome editing is a technique for introducing alterations into specific DNA sequences, such as insertions, deletions, or base substitutions. Several methods are adopted to perform genome editing and clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) systems. Unfortunately, despite substantial progress in understanding the molecular pathways behind obesity, anti-obesity medications are now ineffective. If you are obese, a 10% weight decrease would be preferable to healthy body weight for most people. CRISPR–Cas9, on the other hand, has been shown to reduce body weight by an astonishing 20%. Hence, this updated review elaborates on the molecular basis of obesity, risk factors, types of gene therapy, possible mechanisms, and advantages of the CRISPR–Cas9 system over other methods.

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Data availability

Data availability statement is not applicable for this review.

Abbreviations

AMPK:

Adenosine monophosphate-activated protein kinase

ATS-9R:

9-Mer arginine

BMI:

Basal metabolic index

CCL2:

Chemokine ligands 2

CRISPRa:

Clusters of regularly interspaced short palindromic repeats activation

CRISPR-Cas9:

Clusters of regularly interspaced short palindromic repeats-caspase9

CRISPRi:

Clusters of regularly interspaced short palindromic repeats interference

CrRNA:

Clusters of regularly interspaced short palindromic repeats RNA

DNA:

Deoxyribonucleic acid

DSB:

Double-strand break

epiWAT:

Epididymal white adipose tissue

Fabp4:

Fatty acid-binding protein-4

gRNA:

Guide RNA

GWAS:

Genome-wide association studies

HUMBLE:

Human brown-like fat cells

IL-1β:

Interleukin-1-beta

IL6:

Interleukin-6

LepR:

Leptin receptor

PAM:

Protospacer adjacent motif

POMC:

Proopiomelanocortin

RNA:

Ribonucleic acid

SAM:

Synergistic activation mediator

sgNeg:

Single guide negative

subWAT:

Subcutaneous white adipose tissue

TALENs:

Transcription activator-like effector nucleases

TNF:

Tumor necrosis factor

TracrRNA:

Transactivating clusters of regularly interspaced short palindromic repeats RNA

WHO:

World health organization

ZFN:

Zinc finger nuclease

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Acknowledgements

The authors would like to thank the Tenth People’s Affiliated Hospital of Tongji University for providing the workplace to prepare the review.

Funding

This work was supported by the National Key R&D Program of China (No. 2018YFC1314101, 2016YFC1305600), the National Natural Science Foundation of China (81970677), the Fundamental Research Funds for the Central Universities of Tongji University (22120190210), and Shanghai Committee of Science and Technology, China (19DZ1910200, 18411951803, 17DZ1910603).

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, 200072, China

    Muthukumaran Jayachandran, Zhaoliang Fei & Shen Qu

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  1. Muthukumaran Jayachandran
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  2. Zhaoliang Fei
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  3. Shen Qu
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MJ has written, proofread, and finalized the review; FZL has conceptualized the idea, written and proofread; QS has proofread and approved the study.

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Correspondence to Zhaoliang Fei or Shen Qu.

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This is a review study, and ethical approval is not applicable.

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Jayachandran, M., Fei, Z. & Qu, S. Genetic advancements in obesity management and CRISPR–Cas9-based gene editing system. Mol Cell Biochem 478, 491–501 (2023). https://doi.org/10.1007/s11010-022-04518-w

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