Breakthrough: Transgenic Chicken Blocks H5NI Flu Spread

A transgenic chicken has been developed that blocks transmission of the avian flu to other chickens. The new technique — some aspects of which are not clear even to the geneticists developing it — holds out great promise for preventing human illness as well as unnecessary animal deaths. But nothing is quite that simple when it comes to the genetic “tinkering” of plants and animals; disease resistance is not always enough to overcome public resistance.

Geneticists have been experimenting with animals by slightly altering their genes and cellular chemistry for nearly 50 years. Over that time, attempts have been made to confer resistance to disease onto the very animals that carry that disease. Since the outbreak of H5N1 (avian flu) one decade ago (and several other animal viruses since then), the impetus to develop new techniques to accomplished this has increased.

Many current experiments involve the transplanting of foreign genes, or genetic material (such as RNA), into the ova of the target animal. This “transplanting” is typically accomplished through using a “shuttle” virus (a harmless virus, such as a lentivirus, that has had its genome replaced with a desired one) inserted into the germline cells (ova or sperm) of the animal. The cells take up the virus and allow its Trojan horse-like genetic package (or RNA “cassette”) to be read by the cell’s transcription machinery. The organism thus develops with an altered genome. The result is known as a transgenic animal.

Demonstrating  “proof of concept” of the new technique, a team of scientists lead by Helen Sang, a geneticist at the Roslin Institute of the University of Edinburgh, UK,  created a “genetically modified” chicken that, if infected with the H5N1 virus, cannot infect other chickens.

The new technique — which borrows from another new technique known as RNA interference (RNAi) — uses short pieces of RNA termed short ‘hairpin’ RNAs (shRNAs), to “trick” a key enzyme by bonding with it and somehow preventing it from functioning (i.e., aiding the replication of the virus; see diagram below). Though the infected bird will likely die from the virus, the virus can’t spread it to its cage mates.

Lentiviral Delivery of designed shRNA's and the mechanism of RNA interference in mammalian cells (Dan Cojocari)

This is a different approach to the idea of disease resistance, in that, here the infected animal usually dies from the virus. But because the infected birds can’t spread the virus to others, the contagion is kept in check; a type of resistance is conferred onto the whole population.

On its face, this new technique seems to to be a great way of blocking avian flu and saving perhaps millions of animals from being “culled” (eliminated and slaughtered/disposed of) — a common practice in many developed nations. Though avian flu has not yet spread from human to human, there is a fear that it might do so eventually, and so, this is the preferred way of dealing with outbreaks of animal diseases. Though mostly eradicated in the developed world, H5N1 influenza is still endemic to many developed nations and has killed hundreds of people.

The transgenic chickens are still being tinkered with as researchers seek to confer full resistance (i.e., the birds have no, or a reduced risk, of the virus ever taking hold). But even if they accomplish this goal, there remain several economic and political obstacles before they can be “put into production”.

In much poorer countries, this mass slaughtering is too economically costly and impractical given that agriculture is often spread over many small farms. But the GM birds are also costly; researchers estimate at that it will cost £50,000 (US$79,000) to produce “a small number of stable transgenic birds you can…breed from”.

There are also cultural/religious traditions involved that govern the treatment of birds and prohibit such cullings.

Many poor nations, some with few health regulations, seek to control H5N1 via vaccines, which is an imperfect approach; birds can still develop mild forms of the virus and possibly spread it to healthy birds. And, as always, viruses are quite efficient at avoiding host defenses by virtue of their rapid mutation rates.

With these GM chickens, most of these concerns are surmounted. The GM chickens can be cross-bred to produce birds that carry the shRNA sequence in every cell. It is possible that the targeted enzyme could mutate, but, if this were to happen, it would no longer be able to bind to the virus (to activate it) because its new shape would no longer match binding sites on the virus. In order for the virus to escape its host, both it and the enzyme would need to alter their sequences in eight different locations. This is considered statistically improbable.

GloFish, the first genetically modified animal to be sold as a pet

The researchers have yet to fully explicate that exact mechanism by which the decoy molecule (the shRNA) interferes with the key enzyme (what’s known as the reverse transcriptase enzyme) and thus blocking viral replication and contagion to other birds. Therein lies one of the main obstacles to introducing these birds. Public resistance to GM foods is already significant (more so in Europe than in the U.S.). Convincing folks that they should adopt these transgenic birds because they prevent a disease from spreading — via an unknown, genetic mechanism — is a hard sell.

Other ethical question naturally arise from the fact that the study was funded, in part, by Cobb-Vantress, a major international chicken-breeding company. According to the report in Nature, the company has no plans to continue funding this research project.

So, these birds may never make it to market anyways, However, the new technique, once perfected, could be used to prevent the spread of other animal diseases that also exact a cost from developing world farmers.

Source material for this post came from the Nature article ‘Transgenic chickens curb bird flu transmission’ by Virginia Hughes

Results of these experiments were published in last week’s edition of Science

Top IMAGE – GM chickens could pave way for H5N1-resistant flocks if all political, technical and economic hurdles can be overcome. Image by Norrie Russell, courtesy of Valerie White and The Roslin Institute.

DIAGRAM – (RNA interference)  Dan Cojocari; CC – BY – SA 3.0

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