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From left, Mike Karberg, Alan Lambowitz, and Huatao Guo Usually considered useless stretches of bases, introns are removed from RNA before it is translated into a protein. Now Alan Lambowitz, director of the Institute for Cellular and Molecular Biology at the University of Texas, and his colleagues have put group II introns to good use (H. Guo et al., "Group II introns designed to insert into therapeutically relevant DNA target sites in human cells," Science, 289:452-7, July 21, 2000). Eventual

Aug 21, 2000
Nadia Halim


From left, Mike Karberg, Alan Lambowitz, and Huatao Guo
Usually considered useless stretches of bases, introns are removed from RNA before it is translated into a protein. Now Alan Lambowitz, director of the Institute for Cellular and Molecular Biology at the University of Texas, and his colleagues have put group II introns to good use (H. Guo et al., "Group II introns designed to insert into therapeutically relevant DNA target sites in human cells," Science, 289:452-7, July 21, 2000). Eventually the researchers hope to use introns instead of gene therapy vectors to introduce beneficial genes or disrupt harmful genes in patients. Excised group II introns, found only in bacteria and in organelles of plants, yeast, and fungi, exist in a ribonucleoprotein (RNP) complex with a reverse transcriptase protein that is encoded by the intron. With the help of the RNP complex and cellular machinery, the excised intron RNA inserts directly into a DNA target site and then is reverse transcribed to form a double-stranded version of itself in its new home. A 14-nucleotide portion of the RNP complex is

primarily responsible for recognizing the target DNA. Lambowitz and his colleagues have varied the 14-nucleotide site to recognize many different human and bacterial genes. Bruce Sullenger, associate professor of experimental surgery at Duke University Medical Center, and his colleagues tested whether intron insertion could be carried out in mammalian cells by using lipid vesicles called liposomes to deliver CCR5, a human gene involved in HIV transmission, and a modified intron into cells. PCR analysis of DNA isolated from the mammalian cells showed that the intron had inserted into CCR5, indicating that the mammalian cellular machinery could support this mechanism. Though retargeted group II introns integrate efficiently into chromosomal genes in bacteria, the next step is integrating modified introns into a chromosomal gene in a human cell. "Relatively few people have studied these introns, and not too many were familiar with them. We worked on this as a basic research project ... so the practical application is exciting," says Lambowitz.

--Nadia S. Halim