Editor's Note: Science Scan is a roundup of recently published biotechnology-relevant research

A drug that can powerfully trick a malfunctioning immune system into curing autoimmune disease may well turn out to be carrying the genetic blueprint for human life on earth.

Proof of concept has produced a "tolerizing" DNA-based pharmaceutical to successfully treat experimental autoimmune encephalitis (EAE) - a well-known in vivo model for multiple sclerosis (MS).

The feat is reported in the September 2003 issue of Nature Biotechnology under the title "Protein microarrays guide tolerizing DNA vaccine treatment of autoimmune encephalomyelitis." Its senior author is neuroscientist Lawrence Steinman at Stanford University School of Medicine in Palo Alto, Calif.

Steinman is founder of Bayhill Therapeutics, of Palo Alto. In the article, he and his co-authors showed that one could appropriately and effectively select the autoantigen complementary DNAs to incorporate in expression plasmids to generate tolerizing therapeutics. (Immune tolerance is the ability to endure or be less responsive to a stimulant, especially over a period of continued exposure.)

The research reported in the journal may well represent a breakthrough in the treatment of multiple sclerosis, as well as a foundation for a future of personalized medicines in which DNA will prove the drug of choice.

For the past 10 to 15 years, most research exploring how the immune system might be modulated to provide a positive therapeutics outcome has focused on one of two known aspects of the human immune system - innate and adaptive immunity. The innate activity marshals an immediate, first reaction to foreign invaders for the sole purpose of eliminating them. The less compelling adaptive immune system helps the body develop a memory of "attacks" by foreign substances and thereby provides long-term protection against future insult.

The hallmark of an autoimmune disease such as MS is mounting a protective immune mechanism, which reacts to substances that are neither foreign nor life-threatening but actually are "self" cells and tissues. That is, in autoimmunity the body organizes a defense against itself, against a cell that it should not perceive as a threat, and actually works to destroy or damage healthy tissues as though they were hostile invaders.

Unlike viral vectors or other gene therapy systems, Bayhill Therapeutics relies on DNA encoded to produce a specific antigen and delivered in the form of an intramuscularly delivered plasmid (specialized circular double-stranded DNA) to initiate a cascade of immune events, beginning with the production of a specific antigen and its brief attachment to an antigen-presenting cell. By using DNA that encodes self-antigen, Bayhill believes it is possible to quiet or silence the T-cell response that otherwise would be triggered. Furthermore, that it can do so in a disease-specific way with T-cell populations specific to the disease being treated.

It has evidence in animal models that it can combine novel therapeutic agents to suppress the rouge autoimmune system. Thus, it would strike head on at the root cause of autoimmune diseases, initially in MS but later in rheumatoid arthritis and lupus, among others.

Yeast Converted To Cellular Factories By Adding Unnatural Amino Acids To Its Genetic Code

Revolutionary changes inserted into the genetic code of organisms like yeast allows these cellular factories to mass-produce proteins with unnatural amino acids. A paper titled "An expanded eukaryotic genetic code" appears in the Aug. 15, 2003, issue of Science. A task force of chemists at the Scripps Research Institute in La Jolla, Calif., reports a general method for adding unnatural amino acids to the genetic code of Saccharomyces cerevisiae - baker's yeast.

This yeast, a eukaryotic organism, has cells with membrane-bound nuclei. Earlier studies by the same group incorporated unnatural amino acids in prokaryotic bacterial cells, which lack membrane-bound nuclei. By demonstrating that it is possible to add unnatural amino acids to the yeast's genetic code, the Scripps scientists set the stage for a whole new approach to applying the same technology to other eukaryotic cells, even multicellular organisms. Their feat provides a method for studying and controlling the biological processes that form the basis for some of the most intriguing problems in modern biophysics and cell biology - including signal transduction, intracellular protein trafficking, protein folding and protein-protein interactions.

The five amino acids inserted into the yeast's genetic code include a "benzophenone," an amino acid usable as a photocrosslinker; another photocrosslinker known as an azide; a ketone amino acid that acts like a hook to which other molecules, such as dyes or therapeutics, can be attached; an "iodo" compound that contains a heavy-metal atom, useful for X-ray crystallography; and the amino acid O-methyl-tyrosin, of which the derivatives can be employed in nuclear magnetic resonance imaging.

Day-Night Time Shifts Directly Influence Cell Division In Regenerating Mouse Livers

A newly discovered connection between the body's 24-hour "clock" and the timing of cell division may help oncologists refine the use of certain antitumor drugs, of which the performance seems to be affected by the time of day. Scientists have long suspected a molecular link between these two control systems in mammals. They are prompted by what seems to be a daytime-nighttime variation in the timing of cell growth in perpetually regenerating tissues, such as skin and bone marrow.

Japanese neuroscientists at Kobe University report their findings in Sciencexpress released online Aug. 22, 2003. Their research article is titled "Control mechanism of the circadian clock for timing of cell division in vivo." The authors removed sections of the liver from mice and analyzed the genes involved in the hepatic tissue's regeneration. They observed a 24-hour, or circadian, control over the expression of three key proteins that regulate mitosis. One of these genes, called wee1, was directly regulated by some core components of the circadian time-keeper.