Transgenic sheep generated by lentiviral vectors: Safety and integration analysis of surrogates and their offspring

Kenneth Cornetta, Kimberly Tessanne, Charles Long, Jing Yao, Carey Satterfield, Mark Westhusin

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The safety of HIV-1 based vectors was evaluated during the production of transgenic sheep. Vectors were introduced into the perivitelline space of in vivo derived one-cell sheep embryos by microinjection then transferred into the oviducts of recipient females. At 60-70 days of gestation, a portion of the recipients were euthanized and tissues collected from both surrogates and fetuses. Other ewes were allowed to carry lambs to term. Inadvertent transfer of vector from offspring to surrogates was evaluated in 330 blood and tissue samples collected from 57 ewes that served as embryo recipients. Excluding uterine contents, none of the samples tested positive for vector, indicating that that the vector did not cross the fetal maternal interface and infect surrogate ewes. Evaluating ewes, fetuses and lambs for replication competent lentivirus (RCL); 84 serum samples analyzed for HIV-1 capsid by ELISA and over 600 blood and tissue samples analyzed by quantitative PCR for the VSV-G envelopes revealed no evidence of RCL. Results of these experiments provide further evidence as to the safety of HIV-1 based vectors in animal and human applications.

Original languageEnglish
Pages (from-to)737-745
Number of pages9
JournalTransgenic Research
Volume22
Issue number4
DOIs
StatePublished - Aug 2013

Fingerprint

HIV-1
ewes
Sheep
Lentivirus
Human immunodeficiency virus 1
genetically modified organisms
Safety
sheep
Fetus
Embryonic Structures
fetus
embryo (animal)
lambs
Oviducts
Capsid
Microinjections
sampling
capsid
blood
blood serum

Keywords

  • Embryo microinjection
  • Lentiviral vectors
  • Replication competent lentivirus
  • Transgenic sheep

ASJC Scopus subject areas

  • Biotechnology
  • Genetics
  • Agronomy and Crop Science
  • Animal Science and Zoology

Cite this

Transgenic sheep generated by lentiviral vectors : Safety and integration analysis of surrogates and their offspring. / Cornetta, Kenneth; Tessanne, Kimberly; Long, Charles; Yao, Jing; Satterfield, Carey; Westhusin, Mark.

In: Transgenic Research, Vol. 22, No. 4, 08.2013, p. 737-745.

Research output: Contribution to journalArticle

Cornetta, Kenneth ; Tessanne, Kimberly ; Long, Charles ; Yao, Jing ; Satterfield, Carey ; Westhusin, Mark. / Transgenic sheep generated by lentiviral vectors : Safety and integration analysis of surrogates and their offspring. In: Transgenic Research. 2013 ; Vol. 22, No. 4. pp. 737-745.
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