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Review
. 2020 Dec;20(12):3285-3293.
doi: 10.1111/ajt.16095. Epub 2020 Jul 1.

Applications of CRISPR technologies in transplantation

Affiliations
Review

Applications of CRISPR technologies in transplantation

Cem Kuscu et al. Am J Transplant. 2020 Dec.

Abstract

In transplantation, the ever-increasing number of an organ's demand and long-term graft dysfunction constitute some of the major problems. Therefore, alternative solutions to increase the quantity and quality of the organ supply for transplantation are desired. On this subject, revolutionary Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology holds enormous potential for the scientific community with its expanding toolbox. In this minireview, we summarize the history and mechanism of CRISPR/Cas9 systems and explore its potential applications in cellular- and organ-level transplantation. The last part of this review includes future opportunities as well as the challenges in the transplantation field.

Keywords: animal models: porcine; basic (laboratory) research/science; genomics; immunosuppression/immune modulation; molecular biology; tolerance: chimerism; translational research/science; xenoantigen; xenotransplantation.

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Figures

Figure 1:
Figure 1:. Overview of Cas9-based CRISPR mechanisms.
CRISPR toolbox expands by relying on three versions of Cas9 molecule. (WT: wild type, n: nickase, d: dead (inactive) Cas9, gRNA: guide RNA, PAM: Protospacer Adjacent Motif, me3: methylation of DNA at cytosine, ac: acetylation mark on histones, GFP: green fluorescent protein).
Figure 2:
Figure 2:. On-going and future applications of CRISPR technology for solid organ transplantation.
A) Applications of CRISPR-based technologies at cellular level for tolerance induction. B) CRISPR mediated research strategies. C) Xenotransplantation from CRISPRed transgenic animals and CRISPRed chimeric animal for solid organ. D) Potential ex-vivo CRISPR application for solid organs inside the pump. (ECD: Expanded Criteria Donor, SCNT: Somatic Cell Nuclear Transfer, HSC: hematopoietic stem cell, MSC: Mesenchymal Stem Cell).

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