title: Gene editing as applied to prevention of reproductive porcine reproductive and respiratory syndrome.
abstract: Porcine Reproductive and Respiratory Syndrome (PRRS) causes severe reproductive failure in sows as well as transplacental transfer of PRRS virus (PRRSV) to late-gestation fetuses, resulting in abortions, early farrowing, increased number of stillborn piglets, and weak neonatal piglets. PRRSV-infected boars present with anorexia and lethargy, and have decreased sperm quality. The gene for the cellular receptor that the PRRSV uses, Cluster of differentiation 163 (CD163), was edited using Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene-editing technology to create biallelic DNA edits to the CD163 gene in 100% of the offspring. CD163-null pigs challenged with virus were completely resistant to both Type 1 and Type 2 PRRSV isolates, as measured by clinical signs, viremia, antibody response, and lung histopathology. In vitro studies showed that CD163-null alveolar macrophages were also not permissive to infection by a panel of six Type 1 and nine Type 2 viral isolates. Thus, DNA editing of the CD163 gene prevented PRRSV infection and reproductive losses associated with infection.
authors.affiliation: Division of Animal Science, University of Missouri-Columbia, Columbia, Missouri.
authors.forename: Kristin M
authors.identifier: http://orcid.org/0000-0001-9959-108X
authors.initials: KM
authors.lastname: Whitworth
authors.affiliation: Division of Animal Science, University of Missouri-Columbia, Columbia, Missouri.
authors.forename: Randall S
authors.identifier: http://orcid.org/0000-0002-6012-4035
authors.initials: RS
authors.lastname: Prather
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D005260:Female; D000072669:Gene Editing; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008431:Maternal-Fetal Exchange / Q000235:genetics*; D019318:Porcine Reproductive and Respiratory Syndrome / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D019316:Porcine respiratory and reproductive syndrome virus / Q000235:genetics / Q000472:pathogenicity*; D011247:Pregnancy; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D013552:Swine; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D011956:Receptors, Cell Surface
keywords: CD163; CRISPR/Cas9; genetic engineering; zygote injection