Zinc-finger nuclease will be biopharma’s next focus, says SAFC

By Fiona Barry

- Last updated on GMT

Zinc-finger nuclease will be biopharma’s next focus, says SAFC

Related tags: Dna

Zinc-finger proteins will be at the heart of biomanufacturing innovation in coming years, the head of R&D at SAFC has said.

Kevin Kayser, who oversees media development for large molecule cell cultures, told BioPharma-Reporter.com “Protein quality will be a major focus of the biopharmaceutical industry – in order to match glycosylation patterns for biosimilars, or alter the glycosylation pathways for improved efficacy of the drugs.​”

Zinc-finger nucleases are enzymes which allow scientists to edit the genome of a mammalian cell, knocking out unwanted genes in a more precisely targeted way than past methods.

Kayser was the architect for bringing zinc-finger nuclease technology into the company, when it partnered with gene therapy clinical company Sangamo Biosciences in 2007​.

He described the biopharmaceuticals sector as “a very conservative industry,​” with a continued reliance on early technology with regulatory precedence.

So for example DHFR [dihydrofolate reductase] glutamine synthetase – the glutamine synthetase system was with Lonza for many years and there’s a lot of familiarity with that, and DHFR selection has been used for many years as well.

The enzyme glutamine synthetase can be used to knock out genes responsible for glutamine synthesis and create a glutamine oxytrope, so it has a requirement for that amino acid. Then you can complement that particular mutation by bringing in antibodies or recombinant proteins. It can’t survive unless it receives that particular gene, and we then fool the cells to take along antibodies with it to express those.​”

ZNF’s future

Archie Cullen, President of Bioreliance, SAFC’s biologics testing and manufacturing company, told us SAFC is working with or in talks with many  major pharmaceutical companies about its ZFN platform.

The company can use the technology to create a “ready-to-go​” cell line that performs according to clients’ requests, or it can license the ZFN to the customer and allow them to conduct their own gene editing.

One area of demand for zinc-finger proteins is in preventing apoptosis – the natural death of cells. “When you’re growing them in your bioreactor, at some point the population starts to tail off.​” ZFN can be harnessed to cut out apoptotic genes, he said, allowing cells to live longer and keep producing.

While zinc-finger technology is an improvement on the much cruder gene-editing of the past, the industry anticipates big innovation to come in this area, said Cullen. “The potential there is really quite incredible,​” he said, comparing the possibilities to the leap in cellphone technology in the last twenty years – “it’s almost unrecognisable.​”

Sangamo Biosciences is currently conducting clinical trials using ZFN, with one study in Phase II, focusing on CCR5 genes to target HIV.

Related topics: Upstream Processing

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