Advances in gene modification could lead to disease-resilient livestock

This news article was originally published in the “Research in Edinburgh” section of the Edinburgh University’s Science Magazine Issue 19.

By Lynda-Marie Taurasi

Scientists at the Roslin Institute feel they are on the fast track to producing genetically modified pigs resistant to African Swine Fever.

Genome editing allows scientists to make precise modifications to an organism’s genetic make up. Genome editors allow scientists to make exact edits. These editors are commonly known as “molecular scissors” because they can be used to cut parts of DNA.  There are three types of genome editors:  Transcription activator-like effector nuclease (TALEN), Zinc Finger Nuclease (ZFN), and the most recent and currently being discussed in the media, Crispr-cas9. Both ZFN and TALENs were used in the study, separately, to target against the same gene, and both yielded the same result.

ZFN is expensive and complicated to construct and can target one protein per three DNA letters. TALENS are easier to make and can be made “in house” at the Roslin Institute. It has a 1:1 ratio letter match, which allows for more flexibility to target sequences. Once a “cut” is made, the modification to the cell induces a spontaneous mutation, meaning the cell freaks out and tries to repair itself, which shows that the genome editor worked.

In 2013, the researchers in this study at the Roslin Institute used both the TALEN and ZFN individually into a pig zygote, or fertilized egg, to compare the results, and were able to produce live genome-edited pigs. Pig 26 showed that gene editors were able to precisely edit the genome of a pig zygote by removing exactly one DNA base without any trace of alteration to the rest of the vast genome of the pig. This was a valuable advancement in producing viable livestock resilient to disease.

Nearly three years after Pig 26, Roslin scientists progressed one step further.

Spread by ticks, African swine fever is highly contagious and fatal to farmed pigs. However, the pig’s wild cousin, the warthog, is resistant to the disease, thanks to its genetic make-up. Roslin scientists altered the genetic code of the farmed pigs by editing five letters of the RELA gene, making the allele the same to that of the warthog. They believe the genetic modification is able to produce pigs possibly resistant to the African Swine Fever Virus.

Although the disease has never been found in the UK, outbreaks are rampant in Russia and Sub-Saharan Africa, causing concern among farmers that the disease could spread. Controlled trials are currently underway at the Roslin Institute to test whether the genetically modified pigs are indeed resistant to the disease.