Still Finding Ways to Augment the Existing Management of Acute and Chronic Kidney Diseases with Targeted Gene and Cell Therapies: Opportunities and Hurdles

Abstract

The rising global incidence of acute and chronic kidney diseases has increased the demand for renal replacement therapy. This issue, compounded with the limited availability of viable kidneys for transplantation, has propelled the search for alternative strategies to address the growing health and economic burdens associated with these conditions. In the search for such alternatives, significant efforts have been devised to augment the current and primarily supportive management of renal injury with novel regenerative strategies. For example, gene- and cell-based approaches that utilize recombinant peptides/proteins, gene, cell, organoid, and RNAi technologies have shown promising outcomes primarily in experimental models. Supporting research has also been conducted to improve our understanding of the critical aspects that facilitate the development of efficient gene- and cell-based techniques that the complex structure of the kidney has traditionally limited. This manuscript is intended to communicate efforts that have driven the development of such therapies by identifying the vectors and delivery routes needed to drive exogenous transgene incorporation that may support the treatment of acute and chronic kidney diseases.

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

“…This form of therapy provides a means to treat and prevent the root cause of a given condition. Over the years, several methods have been proposed to elicit efficient gene transfer in various settings ( Corridon, 2022b ; Corridon et al, 2022 ; Davidovic et al, 2022 ; Wang et al, 2022a ; Wang et al, 2022b ; Corridon, 2023 ; Pantic et al, 2023b ; Shakeel and Corridon, 2023 ). However, progress in the development of direct gene transfer methods in the kidney has been limited compared with other organs.…”

“…Recently, plasmid-based hydrodynamic gene delivery has shown promise in overcoming this issue ( Corridon, 2023 ). Therefore, this study aimed to demonstrate the potential of hydrodynamic-based gene delivery to halt progressive or persistent renal function impairment following episodes of ischemia-reperfusion injuries.…”

From waste to wealth: Repurposing slaughterhouse waste for xenotransplantation

“…Another major drawback of these devices is their extracorporeal nature, which renders them prone to infection and thrombosis. Research is also being conducted on devising improved bioreactor systems, identifying alternative gene and cellular approaches to improve cell and tissue regeneration (Hall et al, 2012;Corridon et al, 2013;Collett et al, 2017;Kolb et al, 2018;Corridon et al, 2021;Cai et al, 2022;Shaya et al, 2022;Corridon, 2023a), and employing AI to enhance detection and diagnostics (Shaw and Kirk, 2019;Pantic et al, 2022a;Pantic et al, 2022b;Corridon, 2022;Corridon et al, 2022;Davidovic et al, 2022;Corridon, 2023b;Pantic et al, 2023b).…”

Capturing effects of blood flow on the transplanted decellularized nephron with intravital microscopy

“…Despite the global shortage of organs, transplantation is the best option for those with end-stage renal disease (ESRD), owing to the limitations of dialysis [1][2][3]. The exponential rise in ESRD, characterized by a debilitating and permanent loss of renal function, has heightened the desire for alternatives such as the bioartificial kidney [4,5].…”