Easing process of gene-altering seeds

Chromosome firm looks for partners

By Jon Van
Tribune staff reporter

February 3, 2004

Eager to turn genetic engineering into a manufacturing process, an upstart Chicago biotech firm is developing a technique to make seeds that can withstand poor weather as well as produce pest-resistant crops.

The technology, developed at the University of Chicago, has the potential to provide a powerful new way to re-engineer plants and seeds.

The goal is to create plant strains with many desirable traits--such as a corn plant that grows well in dry soil, resists pests like corn borers and also produces high-protein kernels.

" We've been talking to large seed companies about how we can generate value by helping them get genetically modified seeds to the market faster and enabling them to use fewer plants to express their traits," said Mich Hein, chief executive of Chromatin Inc.

If it works as expected, demand for Chromatin's technology should build as seed companies find more traits they want to introduce in a single hybrid seed, said David McElroy, a vice president with Verdia Inc., a biotech firm based in Redwood City, Calif., that works on gene design.

" Today most seeds feature two or maybe three traits," McElroy said. "The need for this technology will be more urgent when you want more traits."

Chromatin Inc. will soon try to demonstrate the value of its technology by manipulating canola plant genes. It will then move on to other plants such as corn and cotton.

" We know this works in the cells," said Daphne Preuss, a University of Chicago researcher who founded Chromatin.

" Now it's time to prove it works in plants."

Injecting more predictability into genetic engineering would delight researchers at large agricultural companies.

" They're offering a unique solution to a problem that's plagued molecular biology since its inception," said Nathan Danielson, research manager for the National Corn Growers Association. "When you put genes in new tissue with standard techniques, it's a grab bag what type of expression you'll get.

" So, instead of transforming 100 plants, you have to do hundreds or thousands of plants to find the first parent that gives reasonable expression, he said. "We believe Cromatin's technology will allow these genes to be put into a stable environment."

Even though the young company is small, the successes of Preuss' academic research have attracted much industry attention.

" This is on everybody's radar screen," said Tony Cavalieri, recently retired biotech research director for Pioneer Hi-Bred International Inc., the nation's largest seed corn provider. "Daphne's work is really well known in the field."

Preuss, who has been studying the genetic makeup of mustard plants for more than a decade, first created an artificial mustard chromosome to get more precise information.

A chance discovery of a mutant mustard seed and Preuss' understanding of earlier work mapping yeast genes gave her a unique method to study the intricate centers of genes that had long eluded researchers. This enabled Preuss to construct artificial chromosomes to further her studies.

She soon realized the artificial chromosomes could also be used for wholesale genetic manipulation. Her research team has since created artificial chromosomes for several other plants.

If one thinks of a plant's genetic makeup as if it were a book, individual genes would be like sentences while chromosomes are like chapters. Each gene may express a single trait or may work with other genes to express a trait while the chromosome in which they reside provides context and a framework.

Standard genetic engineering inserts one or two designer genes into a cell, letting them land at random in natural chromosomes. Sometimes the genes express the desired trait in the plant, but sometimes they don't. It is really just a matter of luck.

By loading up an artificial chromosome with several designer genes and then inserting it into a plant's DNA, Preuss proposes to cut down on the random nature of the process.

The extra chromosome is accepted easily by a plant and provides a stable platform from which designer genes can manufacture proteins that affect the plant's characteristics, said Preuss.

An added benefit to artificial chromosomes, Cavalieri said, is the predictability they add when new products are reviewed by regulatory agencies.

" It'll help make standard packages the regulatory agencies will be interested in, just because it simplifies things," he said. "You know where the genes go."

Hein is seeking partners for Chromatin who can lend credibility and marketing prowess to promote the technology.

Chromatin will partner with the National Research Council- Plant Biotechnology Institute in Canada to demonstrate how its technology can genetically modify canola, a crop worth about $10 billion worldwide that is used for animal meal, food oils and industrial oils.

" We've developed chromosomes for canola, rape, cabbage and Brussels sprouts and then went on to soybeans, tomatoes and corn," Hein said. "We're now confident we can do it in any plant."