Improved gene expression accelerates biologic drug production

By David Robson

- Last updated on GMT

Related tags: Gene, Dna

Bayer Healthcare is to deploy a new technique, developed by
Millipore, for genetically engineering cells to produce
pharmaceutically useful proteins that could both increase the yield
and accelerate drug production.

The technique works by ensuring the newly inserted genes remain active even if they are placed in dormant parts of the cell's genome. While Bayer Healthcare has already road-tested the technology in its R&D labs, this represents one of the first times the technology has been licensed for large-scale commercial drug production across a pharmaceutical company. The technology will aid the production of biologic drugs, such as coagulation factors and antibodies, which consist of recombinant proteins excreted by genetically engineered clones of mammalian cells held in bioreactors. When engineering these cells, a new gene, responsible for creating the protein, is artificially inserted into the genome of the mammalian cell. Scientists are not able to precisely determine where the gene is placed within the cell's genome, and problems arise when the new gene ends up in a 'dormant' part of the genome. In these areas the DNA is tightly coiled or 'condensed', and the genes do not actively produce proteins. A gene inserted into these regions would be poorly expressed, leading to low yields of the desired proteins. Only a small proportion of a cell's genes, usually responsible for 'housekeeping' activities such as cell division or protein synthesis, are 'open' and active for much of the cells life, meaning the chances that an inserted gene will land in one of the more desirable areas is very small. To improve the yields of biologic drugs, pharmaceutical companies had previously tried to screen through their genetically engineered samples to find the cells with the best protein output, which they would then clone in large quantities to work in the bioreactor. "It's a very lengthy, labour intensive process,"​ John Wynne, the director of business development of the Expression Technologies, Upstream Processing and Bioprocess Division at Millipore told in-PharmaTechnologist.com. "It's like looking for a needle in a haystack.​" Millipore's method, called Ubiquitous Chromatin Opening Element (UCOE) technology, increases the chances that an engineered cell will provide a good yield by ensuring that the inserted gene will remain 'open' and active no matter where it is placed within the genome. "Our technique fills the haystack with needles​," says Wynne. It should also improve the stability and reliability of the gene expression. The company developed the technology by analysing the DNA surrounding the active 'housekeeping' genes to find common structures that may contribute to the gene's prolonged activity. By placing these structures just in front of the inserted gene and its promoter the company found that the genes remain open even if they are surrounded by closed DNA. The full terms of the licensing agreement have not been disclosed, but it is said the agreement included an upfront fee of $5m, to cover both R&D and drug production throughout the company. "We will definitely look into using the technology to improve existing drugs​," says Denise Rennmann, a spokesperson for Bayer Healthcare. The licence will also allow the company to benefit from any improvements Millipore make to the technology in the future. In addition to biologic drug production, it is also hoped that the technique could aid gene therapy, the production of cell-based screens for potential drugs, and the creation of transgenic animals.

Related topics: Upstream Processing

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