A team from the University of Illinois describes a cow that is capable of producing human insulin in her milk. The research published in Biotechnology Journal underscored the importance of this advancement, which the authors contend could usher in a new generation of insulin production. This advancement might translate into an alternative source amid insulin shortages and cost barriers for those challenged with a diabetes diagnosis.

According to Matt Wheeler, professor in the Department of Animal Sciences, part of the College of Agricultural, Consumer and Environmental Sciences at the University of Illinois (U of I), the development of the insulin, produced by a cow, could become eligible for FDA approval for use in humans.

“Mother Nature designed the mammary gland as a factory to make protein really, really efficiently. We can take advantage of that system to produce a protein that can help hundreds of millions of people worldwide,” said Dr. Wheeler. He added, “In the old days, we used to just slam DNA in and hope it got expressed where you wanted it to. We can be much more strategic and targeted these days. Using a DNA construct specific to mammary tissue means there’s no human insulin circulating in the cow’s blood or other tissues. It also takes advantage of the mammary gland’s capabilities for producing large quantities of protein.”

The researchers described the process of developing a cow capable of producing human insulin in her milk. Modified adult fibroblasts were produced via pseudo-lentivirus containing the bovine β-casein promoter and human insulin sequences; these cells were used for nuclear transfer. One successful pregnancy resulting in a transgenic cow was produced from transgenic embryo transfers to recipient cows. In analyzing its milk using western blotting and mass spectrometry, two bands with a molecular mass corresponding to proinsulin and insulin were observed. Mass spectrometry found that human insulin was more present than proinsulin in the milk, and proteases in the transgenic milk were identified that “could onvert proinsulin into insulin and insulin-degrading enzyme that could degrade the recombinant protein.”

“Our goal was to make proinsulin, purify it out to insulin, and go from there. But the cow basically processed it herself. She makes about three to one biologically active insulin to proinsulin,” Dr. Wheeler said. “The mammary gland is a magical thing.”

The authors wrote, “Diabetes is one of the fastest growing global health emergencies. It was estimated that 537 million people had diabetes in 2021, and this number is projected to reach 783 million by 2045.”

The U of I scientists concluded that the increasing worldwide demand for human insulin to treat diabetes could be met through the supply of insulin provided by transgenic animals producing insulin in their milk.

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