REVIEW

Multiple gene modifications of pigs for overcoming obstacles of xenotransplantation

¹ CAS Key Laboratory of Regenerative Biology, Chinese Academy of Sciences, Guangzhou 510530, China
² Research Unit of Generation of Large Animal Disease Models, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College (2019RU015), Beijing 100730, China
³ Sanya Institute of Swine Resource, Hainan Provincial Research Center of Laboratory Animals, Sanya 572000, China
⁴ Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, Wuyi University, Jiangmen 529020, China

^* Corresponding author (email: lai_liangxue@gibh.ac.cn)

Received: 5 May 2023
Revised: 29 August 2023
Accepted: 1 September 2023

Abstract

Xenotransplantation, involving animal organ transplantation into humans to address the human organ shortage, has been studied since the 17th century. Early attempts to obtain organs from animals such as goats, dogs, and non-human primates proved unsuccessful. In the 1990s, scientists agreed that pigs were the most suitable donor animals for xenotransplantation. However, immune rejection between pig and human has hindered the application. To overcome these challenges, researchers developed genetically modified pigs that deactivate xenoreactive antigen genes and express human protective genes. These advances extended xenograft survival from days to years in non-human primates, resulting in the first human heart xenotransplant trial. Using genetically engineered pigs for the organ shortage is promising. This review provides an overview of potential incompatibilities of immunogenicity and functional proteins related to xenotransplantation between humans and pigs. Furthermore, it elucidates possible approaches for multiplex gene modification to breed better-humanized pigs for clinical xenotransplantation.