Adenovirus-mediated gene transfer of human butyrylcholinesterase results in persistent high-level transgene expression in vivo

Nageswararao Chilukuri, Ellen G. Duysen, Kalpana Parikh, Wei Sun, Bhupendra P. Doctor, Oksana Lockridge, Ashima Saxena

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Human serum butyrylcholinesterase (Hu BChE) is a promising therapeutic against the toxicity of chemical warfare nerve agents, pesticide intoxication, and cocaine overdose. However, its widespread application is hampered by difficulties in large-scale production of the native protein from human plasma and/or availability as a recombinant protein suitable for use in vivo. This limitation may be resolved by in vivo delivery and expression of the Hu BChE gene. In this study, recombinant (r) adenoviruses (Ads) encoding full-length and truncated rHu BChEs were tested for in vivo expression in mice. Mice injected with these rAds intraperitoneally failed to express rHu BChE. However, a single tail vein injection of both rAds resulted in persistent high serum levels of rHu BChE in BChE knockout mice, which peaked on days 4/5 at 377 ± 162 U/ml for full-length rHu BChE and 574 ± 143 U/ml for truncated rHu BChE. These activity levels are orders of magnitude higher than 1.9 U/ml of mouse BChE present in wild-type mouse serum. Thereafter, rHu BChE levels dropped rapidly and very little or no activity was detected in the serum 10 days post-virus administration. In conclusion, the present study demonstrates the potential of rAd-mediated Hu BChE gene therapy to counteract multiple lethal doses of chemical warfare nerve agent toxicity.

Original languageEnglish (US)
Pages (from-to)327-331
Number of pages5
JournalChemico-Biological Interactions
Volume175
Issue number1-3
DOIs
StatePublished - Sep 25 2008

Fingerprint

Gene transfer
Butyrylcholinesterase
Transgenes
Adenoviridae
Chemical warfare
Toxicity
Serum
Chemical Warfare Agents
Genes
Plasma (human)
Gene therapy
Cocaine
Viruses
Recombinant Proteins
Pesticides
Availability
Knockout Mice
Genetic Therapy
Tail
Blood Proteins

Keywords

  • Adenovirus
  • Bioscavenger
  • Gene therapy
  • Human butyrylcholinesterase
  • Organophosphorus compounds

ASJC Scopus subject areas

  • Toxicology

Cite this

Adenovirus-mediated gene transfer of human butyrylcholinesterase results in persistent high-level transgene expression in vivo. / Chilukuri, Nageswararao; Duysen, Ellen G.; Parikh, Kalpana; Sun, Wei; Doctor, Bhupendra P.; Lockridge, Oksana; Saxena, Ashima.

In: Chemico-Biological Interactions, Vol. 175, No. 1-3, 25.09.2008, p. 327-331.

Research output: Contribution to journalArticle

Chilukuri, Nageswararao ; Duysen, Ellen G. ; Parikh, Kalpana ; Sun, Wei ; Doctor, Bhupendra P. ; Lockridge, Oksana ; Saxena, Ashima. / Adenovirus-mediated gene transfer of human butyrylcholinesterase results in persistent high-level transgene expression in vivo. In: Chemico-Biological Interactions. 2008 ; Vol. 175, No. 1-3. pp. 327-331.
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