Xenotransplantation: Current Status in Preclinical Research

Lipiński

et al. 2020

Genes

Progress in genetic engineering over the past few decades has made it possible to develop methods that have led to the production of transgenic animals. The development of transgenesis has created new directions in research and possibilities for its practical application. Generating transgenic animal species is not only aimed towards accelerating traditional breeding programs and improving animal health and the quality of animal products for consumption but can also be used in biomedicine. Animal studies are conducted to develop models used in gene function and regulation research and the genetic determinants of certain human diseases. Another direction of research, described in this review, focuses on the use of transgenic animals as a source of high-quality biopharmaceuticals, such as recombinant proteins. The further aspect discussed is the use of genetically modified animals as a source of cells, tissues, and organs for transplantation into human recipients, i.e., xenotransplantation. Numerous studies have shown that the pig (Sus scrofa domestica) is the most suitable species both as a research model for human diseases and as an optimal organ donor for xenotransplantation. Short pregnancy, short generation interval, and high litter size make the production of transgenic pigs less time-consuming in comparison with other livestock species This review describes genetically modified pigs used for biomedical research and the future challenges and perspectives for the use of the swine animal models.

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Application of Genetically Engineered Pigs in Biomedical Research

Lipiński

et al. 2020

Genes

Organ Donation and Transplantation

“…Another important step is the development of "knockout" pigs lacking the 1,3 galactosyl transferase gene encoding enzymes responsible for immunologic expression. Genetic engineering techniques can be easily applied to create rejection-resistant pig organs [6].…”

Section: Xenotransplantationmentioning

confidence: 99%

Future Prospects of Organ Transplantation

Altinors¹

2021

The gap between organ demand and supply is an universal problem in organ and tissue transplantation therapy. The gap is growing in spite of efforts spent in medical, educational, social areas and mass media support. This reality has created the need for completely new therapeutic alternatives for the management of end-stage organ disease. The present research should continue in future aiming to discover systems and devices capable of totally replacing the traditional transplantation. On the other hand, a different progress in underway in transplantation. The indication for solid organ transplantation is to save life and promote quality of life. The new developing transplantations of composite tissue, uterus and face are performed with completely different indications. Facial defects caused by various insults cause serious functional and esthetic disorders, psychological and social problems. Facial transplant surgery is accomplished to overcome such problems. Uterus transplantation is emerging as an alternative to female infertility. Transplantation of composite tissue includes different organs. The main purpose of composite tissue transplantation is to restore reduced or completely lost functions and to increase the quality of life. Nerve regeneration must occur as a consequence of transplant to regain sensory and motor functions. It appears that the future of transplantation involves developments in two main streams; invention of completely new tools for solid organ transplantation and advances in the transplantation of different organs including uterus, face and composite tissue.

Molecular Therapy - Methods & Clinical Development

“…By knockout of genes that activate an immune response and retroviral elements, the aims are to generate organs with reduced hazard of graft rejection and xenozoonosis (an infectious disease transmitted from animal to human), respectively. 343 The ultimate goal of these efforts is to overcome the shortage of human organs such as kidneys, hearts, livers, and lungs for transplantation.…”

Section: Main Textmentioning

confidence: 99%

Ready for Repair? Gene Editing Enters the Clinic for the Treatment of Human Disease

Ernst

Broeders

Herrero-Hernandez

et al. 2020

We present an overview of clinical trials involving gene editing using clustered interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), or zinc finger nucleases (ZFNs) and discuss the underlying mechanisms. In cancer immunotherapy, gene editing is applied ex vivo in T cells, transgenic T cell receptor (tTCR)-T cells, or chimeric antigen receptor (CAR)-T cells to improve adoptive cell therapy for multiple cancer types. This involves knockouts of immune checkpoint regulators such as PD-1, components of the endogenous TCR and histocompatibility leukocyte antigen (HLA) complex to generate universal allogeneic CAR-T cells, and CD7 to prevent self-destruction in adoptive cell therapy. In cervix carcinoma caused by human papillomavirus (HPV), E6 and E7 genes are disrupted using topically applied gene editing machinery. In HIV infection, the CCR5 co-receptor is disrupted ex vivo to generate HIV-resistant T cells, CAR-T cells, or hematopoietic stem cells. In β-thalassemia and sickle cell disease, hematopoietic stem cells are engineered ex vivo to induce the production of fetal hemoglobin. AAV-mediated in vivo gene editing is applied to exploit the liver for systemic production of therapeutic proteins in hemophilia and mucopolysaccharidoses, and in the eye to restore splicing of the CEP920 gene in Leber’s congenital amaurosis. Close consideration of safety aspects and education of stakeholders will be essential for a successful implementation of gene editing technology in the clinic.