Designer organs: The future of personalized transplantation

Abstract

Organ transplantation is the definitive treatment for end‐stage solid organ diseases, yet biological and logistical barriers reduce the rate of successful organ transplants. As such, there is a need for gene therapy and gene modulation strategies in the organ transplantation setting to prevent rejection, expand the donor pool of available organs, and attenuate ischemia‐reperfusion damage. As we are entering an era of “precision medicine,” the organ transplant field is becoming equipped with the tools necessary to personalize and optimize organs designed specifically to withstand injurious pathways that occur during transplantation, such that the concept of “designer organs” will be a reality in the near future. In this review, we highlight the recent progress using gene knockout and knock‐in strategies used mainly in the context of xenotransplantation. We also discuss advancements in CRISPR‐Cas9 gene editing and RNA interference in relation to organ transplantation. Lastly, we discuss the exciting future implications of customized gene therapy in the transplantation setting, and its ability to potentially create a future where organs intended for transplant are personalized to maximize both graft and patient survival.

Wearable and implantable artificial kidney devices for end‐stage kidney disease treatment: Current status and review

“…Xenotransplantation with pigs as source of donor kidneys 92–97 is progressing from experimental studies from pig‐to‐non‐human primates (NHP) to clinical trials with brain‐dead patients. An excellent review on the state‐of‐the‐art of porcine kidney xenotransplantation has been published recently by Cooper et al 93,98 The most important prerequisite for xenotransplantation of porcine organs is the knockout of genes encoding for xenoantigens particularly galactose‐α1, 3‐galactose and other pig cell surface antigens eliciting a strong immune response in primates 98,99 .…”

“…Xenotransplantation with pigs as source of donor kidneys [92][93][94][95][96][97] is progressing from experimental studies from F I G U R E 4 Scheme of an implantable artificial kidney (IAK). The iliac vessels are used as intake of the arterial blood and outlet for the venous blood, while the removed waste is shunted to the bladder.…”

Current Aspects of Xenotransplantation in Human

“…Knocking out the GGTA 1 gene will not only significantly increase the survival length of the patients after the transplantation up to 6 months, but will also highly reduce the hyperacute rejections, as studies of xenotransplantation in baboons suggested [28,29]. Moreover, hyperacute rejection can be further reduced by expression of human complement regulatory proteins such as CD46, CD55, or CD59 together with the GGTA1 deletion [30][31][32]. A more advanced method which is to remove two xeno antigens which are α-Gal and N-glycolylneuraminic acid also can be combined, as it will further reduce the humoral activity compared to a GGTA1 knockout alone [16].…”

Organ Therapeutics During Ex-Situ Dynamic Preservation. A Look Into the Future

“…Among many approaches to ameliorate immune activation of the graft 22 , gene therapy is very appealing because it can specifically target pathways 23,24 , by treating the donor or the graft. Genetic manipulation of donor organs may render grafts more resistant to IRI, reduce immunogenicity and the requirement for systemic immunosuppression, thus promoting long-term graft survival 25 . The combination of gene therapy/modulation during ex-situ organ preservation is relatively new but very promising because it offers a controlled environment and avoid systemic therapy 10 .…”