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Isolation, Culture, and Genetic Engineering of Mammalian Primary Pigment Epithelial Cells for Non-Viral Gene Therapy
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Extensive germline genome engineering in pigs.

Yanan Yue1, Weihong Xu1, Yinan Kan2

  • 1Qihan Bio Inc, Hangzhou, China.

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|September 22, 2020
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Summary
This summary is machine-generated.

Genetically engineered pigs with inactivated porcine endogenous retroviruses (PERVs) show enhanced compatibility for human xenotransplantation. These pigs resist human immune rejection and coagulation issues, paving the way for safer organ transplants.

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Area of Science:

  • Biotechnology
  • Immunology
  • Transplantation

Background:

  • Porcine xenotransplantation is a potential solution for organ shortages.
  • Immune incompatibilities and porcine endogenous retroviruses (PERVs) limit its clinical use.

Purpose of the Study:

  • To genetically engineer pigs for improved compatibility with the human immune system.
  • To address PERVs and enhance immunological and coagulation compatibility for xenotransplantation.

Main Methods:

  • Utilized CRISPR-Cas9 and transposon technologies for extensive genome engineering.
  • Inactivated all PERVs, eliminated three xenoantigens, and introduced nine human transgenes.
  • Assessed physiological parameters, fertility, and germline transmission of edited genes.

Main Results:

  • Produced pigs with all PERVs inactivated and enhanced human compatibility.
  • Engineered pigs demonstrated resistance to human humoral rejection and cell-mediated damage in vitro.
  • Confirmed normal physiology, fertility, and successful germline transmission of 13 genes and 42 alleles.

Conclusions:

  • Extensive genome engineering significantly improves porcine compatibility for human xenotransplantation.
  • These advancements offer a promising path toward safe and effective xenotransplantation procedures.
  • Further research may enable clinical application of these enhanced pigs for organ transplantation.