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. 2012 Dec;47 Suppl 6(Suppl 6):381-6.
doi: 10.1111/rda.12016.

Applying Gene Silencing Technology to Contraception

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Free PMC article

Applying Gene Silencing Technology to Contraception

G A Dissen et al. Reprod Domest Anim. .
Free PMC article

Abstract

Population control of feral animals is often difficult, as it can be dangerous for the animals, labour intensive and expensive. Therefore, a useful tool for control of animal populations would be a non-surgical method to induce sterility. Our laboratories utilize methods aimed at targeting brain cells in vivo with vehicles that deliver a payload of either inhibitory RNAs or genes intended to correct cellular dysfunction. A useful framework for design of a new approach will be the combination of these methods with the intended goal to produce a technique that can be used to non-invasively sterilize cats and dogs. For this approach to succeed, it has to meet several conditions: the target gene must be essential for fertility; the method must include a mechanism to effectively and specifically silence the gene of interest; the method of delivering the silencing agent must be minimally invasive, and finally, the silencing effect must be sustained for the lifespan of the target species, so that expansion of the population can be effectively prevented. In this article, we discuss our work to develop gene silencing technology to induce sterility; we will use examples of our previous studies demonstrating that this approach is viable. These studies include (i) the use of viral vectors able to disrupt reproductive cyclicity when delivered to the regions of the brain involved in the control of reproduction and (ii) experiments with viral vectors that are able to ameliorate neuronal disease when delivered systemically using a novel approach of gene therapy.

Conflict of interest statement

Conflicts of Interest

None of the authors have any conflict of interest to declare.

Figures

Figure 1
Figure 1
Figure Schematic diagram of the research plan summarized in the article. The goal is to use a peptide-modified AAV vector to suppress fertility in cats and dogs. A bacteriophage library is administered by intravenous systemic injection (1) to adult females. The bacteriophage that homes to the hypothalamus is isolated, purified and administered to naïve animals (3). This procedure (termed bio-panning) is repeated until convergence of a single peptide sequence is observed. The DNA coding for the peptide sequence is inserted (4) into the DNA sequence encoding the capsid protein for the AAV vector. An siRNA/miRNA sequence that is the most effective at suppressing expression of the target mRNA in vitro is selected (5), and inserted into the genome of the AAV vector (6). The peptide-modified siRNA/miRNA AAV vector is then administered intravenously (7) to the target species; either cats or dogs. While untreated animals will continue to produce offspring normally, GnRH is reduced in the treated animals resulting in infertility.

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