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Oligonucleotide-based inhibition of embryonic gene expression

Nature Biotechnology volume 17, pages 1184–1187 (1999)Cite this article

Abstract

We describe a technique to define gene function using antisense oligonucleotide (AS-ODN) inhibition of gene expression in mice. A single intravenous injection of an AS-ODN targeting vascular endothelial growth factor (VEGF) into pregnant mice between E7.5–8.5 resulted in a lack of primary angiogenesis. This enabled us to define the critical window required to inhibit VEGF expression and recapitulate the primary loss of function phenotype observed in VEGF (–/–) embryos. This phenotype was sequence-specific and time- and dose-dependent. Injection of an AS-ODN targeting a second gene, E-cadherin, into pregnant mice at E10 confirmed a hypothesized secondary phenotype. This is the first report of AS-ODN inhibition of gene expression in utero and provides a new strategy for target validation in functional genomics.

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Figure 1: Antisense oligonucleotides.
Figure 2: Transplacental delivery of oligonucleotides.
Figure 3: Oligonucleotide-based inhibition of gene expression.

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Author information

Authors and Affiliations

  1. QIK Technology, Inc, Boston, MA

    Samuel E. Driver & Gregory S. Robinson

  2. Ontogeny, Inc, Cambridge, MA

    Jean Flanagan

  3. Department of Ophthalmology, Harvard Medical School Children's Hospital, Boston, MA

    Wei Shen & Lois E.H. Smith

  4. Tanox Biosystems, Inc, Houston, TX

    David W. Thomas

  5. Genzyme Corporation, Cambridge, MA

    Peter C. Roberts

Authors
  1. Samuel E. Driver
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  2. Gregory S. Robinson
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  4. Wei Shen
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  5. Lois E.H. Smith
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  6. David W. Thomas
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  7. Peter C. Roberts
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Correspondence to Samuel E. Driver.

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Driver, S., Robinson, G., Flanagan, J. et al. Oligonucleotide-based inhibition of embryonic gene expression. Nat Biotechnol 17, 1184–1187 (1999). https://doi.org/10.1038/70724

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