Gene Editing: Powerful New Tools for Nephrology Research and Therapy

Miyagi, Ayano; Lu, Aiwu; Humphreys, Benjamin D.

doi:10.1681/asn.2016020146

Cited by 22 publications

(15 citation statements)

References 48 publications

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“…Ultimately, advances in bioengineering, implemented with thoughtful ethical guidance, may yield tissue-specific therapies in humans to abrogate pathogenic AT 1 receptor-mediated actions in the kidney and/or vasculature without invoking off-target immune activation. 108,109 CONCLUSION Complementing its central role in BP homeostasis, the RAS has diverse and complex effects on innate and adaptive immunity. Through coordinated regulation of Ang II levels, the RAS proteolytic cascade affects hemodynamic injury in the heart, kidney, and vasculature leading to profound, global upregulation of inflammatory responses.…”

Section: Immunologic Effects Of Ras Manipulation In Humansmentioning

confidence: 99%

Immunologic Effects of the Renin-Angiotensin System

Crowley

Rudemiller

2017

JASN

130

131

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Inappropriate activation of the renin-angiotensin system (RAS) exacerbates renal and vascular injury. Accordingly, treatment with global RAS antagonists attenuates cardiovascular risk and slows the progression of proteinuric kidney disease. By reducing BP, RAS inhibitors limit secondary immune activation responding to hemodynamic injury in the target organ. However, RAS activation in hematopoietic cells has immunologic effects that diverge from those of RAS stimulation in the kidney and vasculature. In preclinical studies, activating type 1 angiotensin (AT) receptors in T lymphocytes and myeloid cells blunts the polarization of these cells toward proinflammatory phenotypes, protecting the kidney from hypertensive injury and fibrosis. These endogenous functions of immune AT receptors temper the pathogenic actions of renal and vascular AT receptors during hypertension. By counteracting the effects of AT receptor stimulation in the target organ, exogenous administration of AT receptor agonists or angiotensin 1-7 analogs may similarly limit inflammatory injury to the heart and kidney. Moreover, although angiotensin II is the classic effector molecule of the RAS, several RAS enzymes affect immune homeostasis independently of canonic angiotensin II generation. Thus, as reviewed here, multiple components of the RAS signaling cascade influence inflammatory cell phenotype and function with unpredictable and context-specific effects on innate and adaptive immunity.

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Section: Immunologic Effects Of Ras Manipulation In Humansmentioning

confidence: 99%

Immunologic Effects of the Renin-Angiotensin System

Crowley

Rudemiller

2017

JASN

130

131

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“…Commonly used viruses such as lentivirus or adeno-associated viruses do not have tropism to the kidney [41]. In the era of genome-editing with the CRISPR system in vivo [42,43], it has become even more important to optimize and refine renal targeting methods. Hopefully, this bottleneck problem will be overcome in the near future with the emergence of exciting next-generation intracellular delivery technologies [44,45].…”

Section: Discussionmentioning

confidence: 99%

Intravital imaging of the kidney

Hato

Winfree

Dagher

2017

Methods

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Two-photon intravital microscopy is a powerful tool that allows the examination of dynamic cellular processes in the live animal with unprecedented resolution. Indeed, it offers the ability to address unique biological questions that may not be solved by other means. While two-photon intravital microscopy has been successfully applied to study many organs, the kidney presents its own unique challenges that need to be overcome in order to optimize and validate imaging data. For kidney imaging, the complexity of renal architecture and salient autofluorescence merit special considerations as these elements directly impact image acquisition and data interpretation. Here, using illustrative cases, we provide practical guides and discuss issues that may arise during two-photon live imaging of the rodent kidney.

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“…Its development has made possible the realization of new forms of genetic alterations-such as addition, correction, substitution, and ablation-that permanently alter the DNA sequence to insert desired mutations. [1][2][3] With continuous development, gene editing technologies have proven promising for a wide range of activities, such as medicine, agriculture, and food production. 4,5 The emergence of gene editing has become possible with the development of programmable nucleases, which are customized proteins capable of acting on very specific parts of DNA with great precision.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 The emergence of gene editing has become possible with the development of programmable nucleases, which are customized proteins capable of acting on very specific parts of DNA with great precision. 2 The first programmable nuclease used for editing human cells was meganuclease, first used in 1994. Since then other programmable nucleases have been used for this purpose.…”

Section: Introductionmentioning

confidence: 99%

Gene Editing for Treatment and Prevention of Human Diseases: A Global Survey of Gene Editing-Related Researchers

2020

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In the next decades, gene editing technologies are expected to be used in the treatment and prevention of human diseases. Yet, the future uses of gene editing in medicine are still unknown, including its applicability and effectiveness to the treatment and prevention of infectious diseases, cancer, and monogenic and polygenic hereditary diseases. This study aims to address this gap by analyzing the views of over 1,000 gene editing-related researchers from all over the world. Some of our survey results show that, in the next 10 years, DNA double-strand breaks are expected to be the main method for gene editing, and CRISPR-Cas systems to be the mainstream programmable nuclease. In the same period, gene editing is expected to have more applicability and effectiveness to treat and prevent infectious diseases and cancer. Off-targeting mutations, reaching therapeutic levels of editing efficiency, difficulties in targeting specific tissues in vivo, and regulatory and ethical challenges are among the most relevant factors that might hamper the use of gene editing in humans. In conclusion, our results suggest that gene editing might become a reality to the treatment and prevention of a variety of human diseases in the coming 10 years. If the future confirms these researchers' expectations, gene editing could change the way medicine, health systems, and public health deal with the treatment and prevention of human diseases.

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Gene Editing: Powerful New Tools for Nephrology Research and Therapy

Cited by 22 publications

References 48 publications

Immunologic Effects of the Renin-Angiotensin System

Immunologic Effects of the Renin-Angiotensin System

Intravital imaging of the kidney

Gene Editing for Treatment and Prevention of Human Diseases: A Global Survey of Gene Editing-Related Researchers

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