Artificial human chromosome created, researchers report Human cell did the work with 'construction kit'


In a major milestone in the study of human heredity, researchers announced yesterday that they have created the first working, artificial human chromosome, which experts said represents a quantum leap in the ability to probe the complex molecules that make up humankind.

The new technology offers scientists a powerful new research tool for investigating fundamental questions about the chemistry responsible for human heredity, experts said.

Its inventors at Case Western Reserve University and Athersys Inc. hope the techniques also may offer a way to cure inherited diseases by altering a cell's genetic structure -- bypassing biochemical stumbling blocks that have so far stymied efforts to accomplish that task.

In research published in Nature Genetics today, the research team said they were able to use the human cell itself to perform the trickiest portion of creating a synthetic chromosome. The scientists basically gave the cell a molecular construction kit developed after a decade of experiments and let the cell do the actual work of assembling it.

On at least two occasions, the result was a new artificial human chromosome, the researchers reported.

A normal cell has 23 pairs of natural chromosomes -- thread-like structures inherited from an individual's parents that contain the genes that guide the body's gender, growth and development.

Natural chromosomes are built in pieces -- made up of hundreds or thousands of genes, bracketed by protein structures that enhance the structure's stability and guide its functions, turning genes on and off, for example.

Taken altogether, the natural chromosomes contain roughly 100,000 separate genes -- the molecular blueprint for human development.

The artificial chromosome appears to coexist with the natural ones. It appears to divide and multiply normally, surviving as a kind of accessory chromosome for at least six months, the researchers said.

French Anderson, a molecular biologist at the University of Southern California who helped pioneer the concept of human gene therapy, called the new research "a very important advance." The invention of synthetic human chromosomes is, he said, "the next big step."

Officials at Athersys said they hope eventually to use artificial chromosomes as a way to a package treatments for diseases affecting the human immune system such as AIDS, as well as blood disorders such as sickle cell anemia and beta-thalassemia.

Potentially this could be done by packaging a therapeutic gene inside an artificial chromosome either replace a defective gene or generate a medicinal protein.

Anderson, who is working with the pharmaceutical firm Novartis on a competing gene therapy technique, warned that the danger of chromosomal abnormalities may be too high to make artificial chromosomes work as a medical product.

In addition, the manufacturing problems in producing complex chromosomes in industrial quantities may be too formidable, he said.

Pub Date: 4/01/97

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