Gene therapy for kidney disease: targeting cystinuria

Peek, Jennifer L; Wilson, Matthew H.

doi:10.1097/mnh.0000000000000768

Cited by 11 publications

(9 citation statements)

References 40 publications

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“…Such approaches can improve the current understanding of and ways to combat AKI by boosting recovery and halting progression at its inception. Although gene therapy for kidney disease remains a major challenge, new and evolving technologies may actualize treatment for AKI ( Peek and Wilson, 2022 ). Continued and complimentary research to identify new key structural and functional genetic targets, and better examine existing ones while improving gene delivery, will further enhance the utility of genetic medicine as we aim to envision its promise.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous methods have been proposed to deliver exogenous genes to mammalian cells to study and treat human disease ( Friedmann and Roblin, 1972 ; Amiel et al, 2000 ; Niidome and Huang, 2002 ; Chen et al, 2003 ; Appledorn et al, 2008 ; Miyazaki et al, 2009 ; Corridon et al, 2013 ; Collins and Thrasher, 2015 ; Hitchman et al, 2017 ; Kolb et al, 2018 ; Shen et al, 2018 ; Peek and Wilson, 2022 ). With specific regard to the kidney, attempts have been made to protect and repair renal function by targeting single genetic loci ( Lien and Lai, 1997 ).…”

Section: Introductionmentioning

confidence: 99%

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Enhancing the expression of a key mitochondrial enzyme at the inception of ischemia-reperfusion injury can boost recovery and halt the progression of acute kidney injury

Corridon

2023

Front. Physiol.

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Hydrodynamic fluid delivery has shown promise in influencing renal function in disease models. This technique provided pre-conditioned protection in acute injury models by upregulating the mitochondrial adaptation, while hydrodynamic injections of saline alone have improved microvascular perfusion. Accordingly, hydrodynamic mitochondrial gene delivery was applied to investigate the ability to halt progressive or persistent renal function impairment following episodes of ischemia-reperfusion injuries known to induce acute kidney injury (AKI). The rate of transgene expression was approximately 33% and 30% in rats with prerenal AKI that received treatments 1 (T1hr) and 24 (T24hr) hours after the injury was established, respectively. The resulting mitochondrial adaptation via exogenous IDH2 (isocitrate dehydrogenase 2 (NADP+) and mitochondrial) significantly blunted the effects of injury within 24 h of administration: decreased serum creatinine (≈60%, p < 0.05 at T1hr; ≈50%, p < 0.05 at T24hr) and blood urea nitrogen (≈50%, p < 0.05 at T1hr; ≈35%, p < 0.05 at T24hr) levels, and increased urine output (≈40%, p < 0.05 at T1hr; ≈26%, p < 0.05 at T24hr) and mitochondrial membrane potential, Δψm, (≈ by a factor of 13, p < 0.001 at T1hr; ≈ by a factor of 11, p < 0.001 at T24hr), despite elevated histology injury score (26%, p < 0.05 at T1hr; 47%, p < 0.05 at T24hr). Therefore, this study identifies an approach that can boost recovery and halt the progression of AKI at its inception.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enhancing the expression of a key mitochondrial enzyme at the inception of ischemia-reperfusion injury can boost recovery and halt the progression of acute kidney injury

Corridon

2023

Front. Physiol.

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“…Such approaches can improve the current understanding of and ways to combat AKI by boosting recovery and halting progression at its inception. Although gene therapy for kidney disease remains a major challenge, new and evolving technologies may actualize treatment for AKI 36 . Continued and complimentary research to identify new key structural and functional genetic targets, and better examine existing ones while improving gene delivery, will further enhance the utility of genetic medicine as we aim to envision its promise.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous methods have been proposed to deliver exogenous genes to mammalian cells to study and treat human disease [26][27][28][29][30][31][32][33][34][35][36][37] . With specific regard to the kidney, attempts have been made to protect and repair renal function by targeting single genetic loci 38 .…”

Section: Introductionmentioning

confidence: 99%

Enhancing the expression of a key mitochondrial enzyme at the inception of ischemia-reperfusion injury can boost recovery and halt the progression of acute kidney injury

Corridon

2023

Preprint

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Hydrodynamic fluid delivery has shown promise in influencing renal function in disease models. This technique provided pre-conditioned protection in acute injury models by upregulating the mitochondrial adaptation, while hydrodynamic injections of saline alone have improved microvascular perfusion. Accordingly, hydrodynamic mitochondrial gene delivery was applied to investigate the ability to halt progressive or persistent renal function impairment following episodes of ischemia-reperfusion injuries known to induce acute kidney injury (AKI). The rate of transgene expression was approximately 33% and 30% in rats with prerenal AKI that received treatments 1 (T1hr) and 24 (T24hr) hours after the injury was established, respectively. The resulting mitochondrial adaptation via exogenous IDH2 (isocitrate dehydrogenase 2 (NADP+) and mitochondrial) significantly blunted the effects of injury within 24 hours of administration: decreased serum creatinine (» 60%, p < 0.05 at T1hr; » 50%, p < 0.05 at T24hr) and blood urea nitrogen (»50%, p < 0.05 at T1hr; » 35%, p < 0.05 at T24hr) levels, and increased urine output (» 40%, p < 0.05 at T1hr; » 26%, p < 0.05 at T24hr) and mitochondrial membrane potential, Δψm, (» by a factor of 13, p < 0.001 at T1hr; » by a factor of 11, p < 0.001 at T24hr), despite elevated histology injury score (26%, p < 0.05 at T1hr; 47%, p < 0.05 at T24hr). Therefore, this study identifies an approach that can boost recovery and halt the progression of AKI at its inception.

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“…Current gene therapy vectors, such as AAVs and LNPs, have limitations in their ability to target the kidneys effectively. 103,104 This is due in part to the glomerular filtration barrier, which retains many gene vectors, and the complex structure of the kidneys, which makes it difficult to target specific types of kidney cells affected by different genetic kidney diseases.…”

Section: Current Challengesmentioning

confidence: 99%

Gene therapy for pediatric genetic kidney diseases

Song

Sun

et al. 2023

Pediatric Discovery

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Genetic kidney disease is the main cause of chronic kidney disease in children. While the pathogenic genes associated with most genetic kidney diseases have been identified, the underlying mechanisms of disease initiation remain ambiguous, and effective treatment modalities are limited. Gene therapy has emerged as a promising approach for treating genetic diseases. Several gene therapy drugs have been successfully launched to treat genetic diseases affecting the eyes and muscles. However, the development of gene therapy agents for kidney diseases lags behind that of other genetic disorders. In this review, we first comprehensively summarize the main gene therapy strategies. Next, we provide an overview of current treatment options as well as the latest research on gene therapy approaches for pediatric genetic kidney diseases with a particular emphasis on Alport syndrome and polycystic kidney disease. Finally, we discuss the challenges and potential solutions for gene therapy of pediatric genetic kidney diseases.

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Gene therapy for kidney disease: targeting cystinuria

Cited by 11 publications

References 40 publications

Enhancing the expression of a key mitochondrial enzyme at the inception of ischemia-reperfusion injury can boost recovery and halt the progression of acute kidney injury

Enhancing the expression of a key mitochondrial enzyme at the inception of ischemia-reperfusion injury can boost recovery and halt the progression of acute kidney injury

Enhancing the expression of a key mitochondrial enzyme at the inception of ischemia-reperfusion injury can boost recovery and halt the progression of acute kidney injury

Gene therapy for pediatric genetic kidney diseases

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