Genome-wide inactivation of porcine endogenous retroviruses (PERVs)
| Autor: | Rebeca Cortazio, Weihong Xu, Jay A. Fishman, Ellen Shrock, Jürgen Poci, John Aach, Emal Lesha, George M. Church, Haydy George, Dennis Grishin, Robert A. Wilkinson, Marc Güell, Luhan Yang, Dong Niu |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Swine
Xenotransplantation medicine.medical_treatment Molecular Sequence Data Transplantation Heterologous Gene Dosage Endogenous retrovirus Biology Kidney Gene dosage Cell Line medicine Animals Humans Gene Multidisciplinary Base Sequence Endogenous Retroviruses HEK 293 cells Gene targeting Epithelial Cells Genes pol Virology Transplantation HEK293 Cells Cell culture Gene Targeting Virus Inactivation CRISPR-Cas Systems Retroviridae Infections |
| Zdroj: | Science. 350:1101-1104 |
| ISSN: | 1095-9203 0036-8075 |
| Popis: | The shortage of organs for transplantation is a major barrier to the treatment of organ failure. Although porcine organs are considered promising, their use has been checked by concerns about the transmission of porcine endogenous retroviruses (PERVs) to humans. Here we describe the eradication of all PERVs in a porcine kidney epithelial cell line (PK15). We first determined the PK15 PERV copy number to be 62. Using CRISPR-Cas9, we disrupted all copies of the PERV pol gene and demonstrated a >1000-fold reduction in PERV transmission to human cells, using our engineered cells. Our study shows that CRISPR-Cas9 multiplexability can be as high as 62 and demonstrates the possibility that PERVs can be inactivated for clinical application of porcine-to-human xenotransplantation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|