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Molecular machine may lead to new drugs to combat human diseases

The crystallized form of a molecular machine that can cut and paste genetic material is revealing possible new paths for treating diseases such as some forms of cancer and opportunistic infections that plague HIV patients.

Purdue University researchers froze one of these molecular machines, which are chemical complexes known as a Group I intron, at mid-point in its work cycle. When frozen, crystallized introns reveal their structure and the sites at which they bind with various molecules to cause biochemical reactions. Scientists can use this knowledge to manipulate the intron to splice out malfunctioning genes, said Barbara Golden, associate professor of biochemistry. Normal genes then can take over without actually changing the genetic code.

The results of the Purdue study are published in the January issue of the journal Nature Structural and Molecular Biology.


"In terms of human health, Group I introns are interesting because they cause their own removal and also splice the ends of the surrounding RNA together, forming a functional gene," Golden said. "We can design introns and re-engineer them so they will do this to RNA in which we're interested."

Once thought of as genetic junk, introns are bits of DNA that can activate their own removal from RNA, which translates DNA's directions for gene behavior. Introns then splice the RNA back together. Scientists are just learning whether many DNA sequences previously believed to have no function actually may play specialized roles in cell behavior.

While humans have introns, they don't have Group I introns. Many pathogens that cause human diseases, however, do have Group I introns, including the HIV opportunistic infections pneumocystis, a form of pneumonia, and thrush, an infection of tissues in the oral cavity. This makes introns a potential target for therapeutics against these diseases by using a strategy called targeted trans-splicing in which introns are manipulated t
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Source:Purdue University


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