CRISPR/Cas9 gene-editing technology, a way to generate very precise gene knock-out kits, has now been used to produce cows with resistance to bovine tuberculosis.

Bovine TB, caused by Mycobacterium bovis, can be transmitted from livestock to humans, primarily if raw milk is consumed (just one reason to embrace post-1860 science about food, namely pasteurization), and even other animals. 

The researchers inserted the NRAMP1 gene into the genome of bovine fetal fibroblasts -- a cell derived from female dairy cows -- using CRISPR/Cas9n. These cells were then used as donor cells in somatic cell nuclear transfer, which the Obama administration has refused to allow in the U.S. but is legal in China. In SCNT, the nucleus of a donor cell carrying the new gene is inserted into an egg cell, known as an ovum, in this case a female cow. Ova were nurtured in the lab into embryos before being transferred into mother cows for a normal pregnancy cycle. The experiments were also conducted using the standard CRISPR/Cas9 technology as a comparison.


 Source: Badgers and Bovine TB: Government response to the EFRA Select Committee’s Tenth Report of 2007 - 2008

A total of 11 calves with new genes inserted using CRISPR were able to be assessed for resistance to tuberculosis and any off target genetic effects. Genetic analysis of the calves revealed that NRAMP1 had successfully integrated into the genetic code at the targeted region in all of the calves. None of the calves that had the gene inserted using the new CRISPR/Cas9n technology had any detectable off target effects whereas all of the calves with the gene inserted with previously used techniques for CRISPR/Cas9 did.

When the calves were exposed to M. bovis, the bacterium that causes bovine tuberculosis, the researchers found that transgenic animals showed an increased resistance to the bacteria measured by standard markers of infection in a blood sample. They also found that white blood cells taken from the calves were much more resistant to M. bovis exposure in laboratory tests.

Though bovine TB has killed more cows than all other diseases combined, anti-science groups like Friends of the Earth want all biological technology banned, even it means cruelty to animals, and have lobbied the U.S. government aggressively to prevent its use.

Yong Zhang et al., Single Cas9 nickase induced generation of NRAMP1 knockin cattle with reduced off-target effects, Genome Biology February 2017 DOI: 10.1186/s13059-016-1144-4