Leptin gene-targeted editing in ob/ob mouse adipose tissue based on the CRISPR/Cas9 system

Zhu, Lin; Yang, Xiaoyan; Li, Juyi; Xiong, Jun; Bai, Xiangli; Zhao, Ying; Cheng, Wenzhuo; Shu, Meng; Zhu, Yan; Jin, Si

doi:10.1016/j.jgg.2021.01.008

Cited by 10 publications

(4 citation statements)

References 34 publications

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“…Second, in vivo editing, where the CRISPR cargos are injected systemically or locally. The latter approach has been applied in leptin-deficient, obese ob / ob mice using an adenoviral CRISPR system injected locally into white adipose tissue 166 . Although less than 2% of alleles were repaired, the production of leptin and its physiological functions, such as inhibition of food intake, were restored.…”

Section: Innovative Treatment Approachesmentioning

confidence: 99%

The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits

Körner

Fischer‐Posovszky

2022

Nat Rev Endocrinol

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Obesity is a multifactorial and complex disease that often manifests in early childhood with a lifelong burden. Polygenic and monogenic obesity are driven by the interaction between genetic predisposition and environmental factors. Polygenic variants are frequent and confer small effect sizes. Rare monogenic obesity syndromes are caused by defined pathogenic variants in single genes with large effect sizes. Most of these genes are involved in the central nervous regulation of body weight; for example, genes of the leptin–melanocortin pathway. Clinically, patients with monogenic obesity present with impaired satiety, hyperphagia and pronounced food-seeking behaviour in early childhood, which leads to severe early-onset obesity. With the advent of novel pharmacological treatment options emerging for monogenic obesity syndromes that target the central melanocortin pathway, genetic testing is recommended for patients with rapid weight gain in infancy and additional clinical suggestive features. Likewise, patients with obesity associated with hypothalamic damage or other forms of syndromic obesity involving energy regulatory circuits could benefit from these novel pharmacological treatment options. Early identification of patients affected by syndromic obesity will lead to appropriate treatment, thereby preventing the development of obesity sequelae, avoiding failure of conservative treatment approaches and alleviating stigmatization of patients and their families.

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Section: Innovative Treatment Approachesmentioning

confidence: 99%

The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits

Körner

Fischer‐Posovszky

2022

Nat Rev Endocrinol

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“…Research is thankfully still producing new solutions. Patients with monogenic forms of obesity may benefit in the future from CriSPr-mediated gene editing via induced pluripotent stem cell technologies ( 88 ) or direct defective gene repairing ( 89 ). Given the clinical severity of these patients, involvement and cooperation from both physicians and scientists is still required to improve their conditions and outcomes.…”

Section: Discussionmentioning

confidence: 99%

Current Treatments for Patients with Genetic Obesity

Faccioli¹,

Poitou²,

Clément³

et al. 2023

Jcrpe

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Obesity derives from impaired central control of body weight, implying interaction between environment and an individual genetic predisposition. Genetic obesities, including monogenic and syndromic obesities, are rare and complex neuro-endocrine pathologies where the genetic contribution is predominant. Severe and early-onset obesity with eating disorders associated with frequent comorbidities make these diseases challenging. Their current estimated prevalence of 5-10% in severely obese children is probably underestimated due to the limited access to genetic diagnosis. A central alteration of hypothalamic regulation of weight implies that the leptin-melanocortin pathway is responsible for the symptoms. The management of genetic obesity has so far been only based, above all, on lifestyle intervention, especially regarding nutrition and physical activity. New therapeutic options have emerged in the last years for these patients, raising great hope to manage their complex situation and improve quality of life. Implementation of genetic diagnosis in clinical practice is thus of paramount importance to allow individualized care. This review describes the current clinical management of genetic obesity and the evidence on which it is based. Some insights will also be provided into new therapies under evaluation.

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“…Interestingly, in a recent study, the mutated leptin gene in ob/ob mice was edited using CRISPR/Cas9. The ob/ob mice displayed a correction of 1.67% of leptin alleles, which was sufficient to restore the production and function of leptin [103]. Moreover, regulating the expression of obesity-causing genes, like MC4R, by using the CRISPRi technique gene expression has also been suggested to be useful in genetic obesity therapy [104].…”

Section: Other Current and Promising Therapeutic Approachesmentioning

confidence: 99%

Syndromic and Monogenic Obesity: New Opportunities Due to Genetic-Based Pharmacological Treatment

Kalinderi,

Goula,

Sapountzi

et al. 2024

Children

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Obesity is a significant health problem with a continuously increasing prevalence among children and adolescents that has become a modern pandemic during the last decades. Nowadays, the genetic contribution to obesity is well-established. For this narrative review article, we searched PubMed and Scopus databases for peer-reviewed research, review articles, and meta-analyses regarding the genetics of obesity and current pharmacological treatment, published in the English language with no time restrictions. We also screened the references of the selected articles for possible additional articles in order to include most of the key recent evidence. Our research was conducted between December 2022 and December 2023. We used the terms “obesity”, “genetics”, “monogenic”, “syndromic”, “drugs”, “autosomal dominant”, “autosomal recessive”, “leptin-melanocortin pathway”, and “children” in different combinations. Recognizing the genetic background in obesity can enhance the effectiveness of treatment. During the last years, intense research in the field of obesity treatment has increased the number of available drugs. This review analyzes the main categories of syndromic and monogenic obesity discussing current data on genetic-based pharmacological treatment of genetic obesity and highlighting the necessity that cases of genetic obesity should follow specific, pharmacological treatment based on their genetic background.

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Leptin gene-targeted editing in ob/ob mouse adipose tissue based on the CRISPR/Cas9 system

Cited by 10 publications

References 34 publications

The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits

The promise of new anti-obesity therapies arising from knowledge of genetic obesity traits

Current Treatments for Patients with Genetic Obesity

Syndromic and Monogenic Obesity: New Opportunities Due to Genetic-Based Pharmacological Treatment

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