May 1, 2016 (Vol. 36, No. 9)

The Baculovirus Can Be Used to Deliver a Beneficial Engineered Gene into a Cultured Insect Cell and Express a Therapeutic Protein or Antibody

The U.S. Forest service notes that, “the gypsy moth, Lymantria dispar, is one of North America’s most devastating forest pests,” capable of chewing through millions of acres of forest in a year. People have been trying to control the pest for more than 100 years, and the battle took a biotech turn in the 1980s when researchers began working with a virus that infected the dreaded moth.

It was a baculovirus, and soon it was engineered to be a Trojan Horse that carries a deadly gene into the moths. The technology worked flawlessly and precisely. This baculovirus infects only moths, no other organisms, and causes no harm to humans. Today, a baculovirus-based product is used in some areas to control the gypsy moth population.

The precision of the baculovirus technology was soon adapted for bioprocessing. Instead of delivering a toxic gene to a whole organism, the baculovirus can be used as a vector to deliver a beneficial engineered gene into a cultured insect cell and express a therapeutic protein or antibody.

Insects are animals, so their cells provide a eukaryotic environment that can express large proteins with the post-translational modifications so important for many therapeutic applications.

Today, insect cell based biomanufacturing is growing in popularity because it is a less complex system for production of many proteins, antibodies, and vaccines. For example, insect cells grow well at room temperature, without CO2, so the culturing process is simpler and more cost-effective. I believe in the near term we will see insect cell based bioprocessing grow into a fertile middle ground, in between microbial fermentation and traditional mammalian cell culture systems.

Gypsy moths, such as the male and female adults shown in this image, can cause widespread defoliation, damaging valuable woodlands and exposing vulner- able bird species to predation. Efforts to prevent infestations include biotech intervent- ions, some of which have been adapted for their bioprocessing advantages. [John H. Ghent USDA Forest Service,]

Single-Use Platforms

For newer companies, starting with an insect cell, single-use platform lowers the costs of entry and operations. Connecticut-based Protein Sciences is an early leader in this regard, being the first to secure FDA approval for a new generation of flu vaccine made by insect cell processes. Established companies with mammalian cell-based infrastructure can look toward a hybrid model of production and shift some of their development pipeline toward insect cell culture.

For these reasons, we have added an insect cell program to our curriculum at the Worcester Polytechnic Institute’s Biomanufacturing Education & Training Center to give people an opportunity to work with the technology hands-on and evaluate how it may be applicable to their business plan.

As the biopharmaceutical industry evolves, with disruptive new technologies, the advent of biosimilars, and the growing ability to target smaller patient populations with rare disease therapies all putting significant cost pressures on legacy mammalian cell-based manufacturing operations, insect cell culture systems can play an important role.

In other words, it’s a good time to be thinking about bugs.

Kamal Rashid, Ph.D. ([email protected]), is the director of the Biomanufacturing Education & Training Center at WPI and a co-chair of the MassBio Biomanufacturing working group.

Previous articleHow Cancer Cells Slide along Narrow Path to Metastasis
Next articleTop 10 U.S. Biopharma Clusters 2016