Low allergy milk from engineered cow – experts respond

New Zealand scientists have genetically engineered a cow to produce milk lacking beta-lactoglobulin, a protein to which some people are allergic .

Researchers from Agresearch and the University of Waikato used  RNA interference, a process that stops target genes from producing proteins, to engineer a dairy cow capable of producing milk lacking the whey protein beta-lactoglobulin (BLG). 

BLG is one of several proteins that can cause a reaction in people with allergies to milk proteins.

Inhibition of the gene which produces beta-lactoglobulin was developed first in cells and then tested in a mouse model before being incorporated in to a genetically engineered calf. Milk from the cow contained no trace of BLG but did exhibit increased levels of other milk proteins such as casein. 

The study is published today in Proceedings of the National Academy of Sciences. More information can be found in this press release from Agresearch.

The Science Media Centre contacted experts for comment on the research. Feel free to use these quotes in your reporting. To follow up, please contact the SMC (04 499 5476; smc@sciencemediacentre.co.nz). 

Dr Mike Boland, Principal Scientist and Executive Officer, Riddett Institute, comments:

“This is an exciting and interesting piece of work.  Beta-lactoglobulin is the major whey protein in bovine milk, making up about half the whey protein or 10% of the total protein in cows’ milk.  The role of beta-lactoglobulin in the milk of some species has never been properly understood – it does not occur in human milk – and a true purpose of this protein has never been found; yet there are no reports in the scientific literature of bovine milk occurring without it.

“The fact that these scientists have produced a viable calf that does not produce this protein is therefore scientifically very interesting.  Any commercial potential of this knockout is still some distance away.  Although the composition of milk from this experimental animal has been shown to be quite unusual, this composition must be viewed with caution, as it was artificially produced (induced by hormones) rather than from natural lactation.  It also remains to be seen if this animal is able to breed.

“Beta-lactoglobulin has long been regarded as the major allergen in cows’ milk and so a niche opportunity must exist for milk such as this, for use in hypoallergenic infant formulas and the like.  The absence of beta-lactoglobulin also has the potential to improve some processing properties of milk.  This protein, however, is the main source of branched-chain amino acids in whey, and these are important for muscle metabolism – which is why whey powders are favoured by sports people and body builders.  It is also the source of gelling functionality in whey products.  And, of course, most people are not allergic to cows’ milk.  There is therefore not a case for getting rid of beta-lactoglobulin from all milk.”

Assoc Prof Rohan Ameratunga, Adult and Paediatric Immunologist, Auckland City Hospital, comments:   

“The study aimed to reduce the level of Beta lactoglobulin in bovine milk with a view reducing the allergenicity of milk.  The group have used cutting edge technology to inhibit expression of the bovine Beta lactoglobulin gene.  They should be congratulated for their innovative technology.

“It should however be noted cow’s milk allergy may result from IgE antibodies to a variety of proteins.  Our own work has shown Beta lactoglobulin is a major allergen.  However many patients with cow’s milk allergy generate IgE antibodies to other proteins including alpha lactalbumin, caseins etc.

“The absence of Beta lactoglobulin would therefore not be a guarantee patients with cow’s milk allergy could consume this product safely. ”

From the UK SMC:

Prof Bruce Whitelaw, Professor of Animal Biotechnology at the University of Edinburgh, said:

“Milk is a major source of protein for humans across many parts of the world; however, there is a relatively high incidence of allergic reactions to proteins in milk.  The authors convincingly demonstrate that RNA interference (RNAi) technology can be combined with transgenic or GM technology to produce cattle with minimal levels of the major milk allergen beta-lactoglobulin.  This reduction of one milk protein level was accompanied by an increase in others, namely the caseins.  This is notable since it represents one of the few RNA interference success stories in mammals and offers a good example of how these technologies can be used to provide alternative strategies to current manufacturing process

“RNAi has a long history of successful application in diverse species from plants to worm – this is the first spectacular report for livestock.  RNAi knocks down gene activity, i.e. it reduces gene activity without eliminating it. In this study beta-lactoglobulin levels are reduced to only 5% of original levels.  There are currently projects that are attempting to knock out beta-lactoglobulin in livestock which should reduce this protein levels to zero.  Theoretically RNAi offers fine tuning in comparison to knock out strategies.

“Time will tell how widely applicable RNA interference will be in GM livestock – but this is certainly a milestone study in this field.  It is likely, however, that different applications of the emerging DNA editor technologies (e.g. TALENs and ZFNs) will provide even more elegant strategies for genome engineering that combine target site specificity with the ability to fine tune expression levels that do not fall under the ‘transgenic’ banner in the near future.”