Transplastomic Plants -- A New Plant Transgenic

A paper in the March Nature Biotechnology by Monsanto (St. Louis) scientists shows how plant choloroplasts can be turned into protein factories. Targeting the gene for human somatotropin (hST) to tobacco chloroplasts, the scientists achieved active, therapeutic protein at levels 300-fold higher than those obtained with nuclear transgenics, accounting for nearly 7% of the soluble protein of the plant.

Until now, most genetic engineering has focused on introducing foreign genes into nuclear DNA. However, nuclear transgene expression isn't guaranteed, as the incoming DNA integrates randomly into chromosomal DNA, often inserting into silent regions. This necessitates screening multiple transgenic plants for those with decent expression levels. Chloroplasts, on the other hand, have a simple genome into which directed integration can be done, which greatly increases the likelihood of high expression. Furthermore, a plant call has many thousands of copies of chloroplast DNA, providing a built in amplification system for the transgene.

In the present work, Jeffrey Staub and his colleagues produced the human therapeutic hormone hST, the hormone used to treat hypopituitary dwarfism in children. Human somatotropin is currently produced commercially in genetically engineered bacteria, a conventional, but costly, approach widely used to produce some pharmaceuticals.

In addition to finding high expression levels in the transplastomic plants, as they're called, the researchers found that crosses between these genetically modified plants and wild-type tobacco yielded offspring that had no inserted genes within their nuclear or chloroplast DNA. Furthermore, the authors could detect no foreign genes within the pollen of transgenic plants, which makes them environmentally friendly.

The ability to produce high levels of hST in tobacco plants with engineered chloroplasts could significantly reduce the cost of manufacturing the therapeutic, reduces the risk of foreign gene transfer to weedy relatives in the environment, and avoids the risk of viral contamination that can occur when recombinant protein is produced in mammalian cell culture.

"Conventional production means are costly, and what the genetic engineering of plastids may offer is a less expensive, more efficient way to produce important pharmaceutical proteins," said Jeffrey Staub, manager of the Plastid Transformation Program for Monsanto and primary author of the Nature Biotechnology paper. "This, in turn, could eventually lead to lower-cost drugs that might help make such life-saving medicines more accessible to those who need them."

For more information: Jeffrey M. Staub, Monstanto Co., 700 Chesterfield Parkway North, BB3G, St. Louis, MO 63198. Tel: 314-737-6645. Fax: 314-737-5223. Email: jeffrey.m.staub@monsanto.com.

By Laura DeFrancesco