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Small interfering RNAs target HIV
MEDICINE AND HEALTH POLICY
Could 40 winks provide more than a battery recharge? not without its critics, however. “Some of the studies on the involvement of REM and other types of sleep in learning are contradictory”, says Jerry Siegel (University of California, Los Angeles, CA, USA). “Furthermore, individuals who get no REM sleep because of brain damage or drug-induced sleep suppression do not have any learning deficits.” In their new work, Mednick and co-workers asked whether daytime napping affects learning. 73 people were tested for their ability to do a visual texture discrimination test at 0900 h and 1900 h, and at 0900 the next day. Some of the “guineapigs” took 60 or 90 min naps in the early afternoon, the rest went about
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
Science Photo Library
n afternoon siesta may be more than just a pleasant way to sleep off lunch. A 60–90 min early afternoon nap, say Sara Mednick (Salk Institute, La Jolla, CA, USA) and her Harvard colleagues, can improve perceptual skill learning as much as a full night’s sleep. “A short nap can be a real pick-me-up”, says Mednick, “and now it seems that a long nap may even help you to learn”. According to the memory consolidation theory, sleep processes, in particular REM sleep, somehow fix memory traces and thus aid learning. For example, explains Mednick, data show that learning a visual task needs at least 6 h nocturnal sleep. This theory of learning is
A
REM sleep is needed to help learning
their normal business (Nat Neurosci; published online June 22; DOI 10.1038/nn1078).
Small interfering RNAs target HIV NA interference mediated by small interfering RNAs (siRNAs) is a potent gene-silencing mechanism, and a preliminary study in mice has shown that this technology may be a useful therapeutic approach for HIV-1 infection. “This is the first demonstration of siRNAs being functionally expressed as haemopoietic progenitor cells, and these cells were allowed to differentiate into macrophages ex vivo, and T lymphocytes in vivo”, says lead researcher John Rossi, from the City of Hope’s Beckman Research Institute (Duarte, CA, USA). “In both cases, they were normal compared with controls that weren’t expressing siRNAs, and we were able to get good T-lymphocyte differentiation in the SCID-hu mouse animal models.” The researchers introduced an anti-Rev siRNA construct into CD34+ haemopoietic progenitor cells, using an HIV-based lentiviral vector. The cells then underwent normal differentiation, maturing into macrophages in vitro and into T cells in SCID-hu mouse thy/liv grafts. Both the T cells and the macrophages showed marked resistance to the HIV-1 virus. (Mol Ther; published online May 21; DOI:10.1016/S1525-0016 (03)00140-0). The researchers were concerned about safety, explains Rossi, because they were
R
interfering with a natural cellular mechanism. “We didn’t know if the haemopoetic cells would still undergo normal differentiation, and if they did, both in cell culture and in-vivo, if their progeny would still be functionally capable of using the programmed siRNAs to knock out HIV.” Rossi and colleagues hope to be able to move to human trials within the next year, possibly targeting patients who have failed drug therapy but who still have enough T cells to ward off opportunistic infections. There are many aspects of RNA interference that could be of benefit in the treatment of HIV infection, says Mario Stevenson (University of Massachusetts Medical School, Worcester, MA, USA). “The process targets RNA and not protein so RNA interference could be used to attack viruses that are resistant to all of the current inhibitors.” It is very likely that HIV would rapidly develop resistance to individual siRNAs because RNA interference is so sequence-specific, he adds. “So the next step will be to determine if different siRNAs can be expressed in the same cell since it will be harder for the virus to become resistant to multiple individuals simultaneously.”
People who did not nap did worse in the evening than the morning. “It’s like playing a piano piece continuously”, says Mednick. “You get worse as you get more tired.” By contrast, those who had a nap that included slow wave sleep retained good performance all day although they still did not learn. For that, explains Mednick, “a full cycle of slow wave and REM sleep was needed. Then their short daytime sleep improved learning as much as a full night’s sleep.” Siegel’s scepticism about the memory consolidation theory is not lessened by this new study. “I suspect that the people who had napped did better in the evening test simply because they were less sleepy”, he suggests. This was unlikely to be the case, counters Mednick, because when participants were tested in one visual quadrant and then retested later in the contralateral quadrant, both the deterioration in “non-nappers” and the improvement in “nappers” disappeared. Thus, she concludes, “our results cannot be explained by fatigue or otherwise of the whole person”.
Roxanne Nelson Jane Bradbury
2214
THE LANCET • Vol 361 • June 28, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet
Could 40 winks provide more than a battery recharge? not without its critics, however. “Some of the studies on the involvement of REM and other types of sleep in learning are contradictory”, says Jerry Siegel (University of California, Los Angeles, CA, USA). “Furthermore, individuals who get no REM sleep because of brain damage or drug-induced sleep suppression do not have any learning deficits.” In their new work, Mednick and co-workers asked whether daytime napping affects learning. 73 people were tested for their ability to do a visual texture discrimination test at 0900 h and 1900 h, and at 0900 the next day. Some of the “guineapigs” took 60 or 90 min naps in the early afternoon, the rest went about
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
Science Photo Library
n afternoon siesta may be more than just a pleasant way to sleep off lunch. A 60–90 min early afternoon nap, say Sara Mednick (Salk Institute, La Jolla, CA, USA) and her Harvard colleagues, can improve perceptual skill learning as much as a full night’s sleep. “A short nap can be a real pick-me-up”, says Mednick, “and now it seems that a long nap may even help you to learn”. According to the memory consolidation theory, sleep processes, in particular REM sleep, somehow fix memory traces and thus aid learning. For example, explains Mednick, data show that learning a visual task needs at least 6 h nocturnal sleep. This theory of learning is
A
REM sleep is needed to help learning
their normal business (Nat Neurosci; published online June 22; DOI 10.1038/nn1078).
Small interfering RNAs target HIV NA interference mediated by small interfering RNAs (siRNAs) is a potent gene-silencing mechanism, and a preliminary study in mice has shown that this technology may be a useful therapeutic approach for HIV-1 infection. “This is the first demonstration of siRNAs being functionally expressed as haemopoietic progenitor cells, and these cells were allowed to differentiate into macrophages ex vivo, and T lymphocytes in vivo”, says lead researcher John Rossi, from the City of Hope’s Beckman Research Institute (Duarte, CA, USA). “In both cases, they were normal compared with controls that weren’t expressing siRNAs, and we were able to get good T-lymphocyte differentiation in the SCID-hu mouse animal models.” The researchers introduced an anti-Rev siRNA construct into CD34+ haemopoietic progenitor cells, using an HIV-based lentiviral vector. The cells then underwent normal differentiation, maturing into macrophages in vitro and into T cells in SCID-hu mouse thy/liv grafts. Both the T cells and the macrophages showed marked resistance to the HIV-1 virus. (Mol Ther; published online May 21; DOI:10.1016/S1525-0016 (03)00140-0). The researchers were concerned about safety, explains Rossi, because they were
R
interfering with a natural cellular mechanism. “We didn’t know if the haemopoetic cells would still undergo normal differentiation, and if they did, both in cell culture and in-vivo, if their progeny would still be functionally capable of using the programmed siRNAs to knock out HIV.” Rossi and colleagues hope to be able to move to human trials within the next year, possibly targeting patients who have failed drug therapy but who still have enough T cells to ward off opportunistic infections. There are many aspects of RNA interference that could be of benefit in the treatment of HIV infection, says Mario Stevenson (University of Massachusetts Medical School, Worcester, MA, USA). “The process targets RNA and not protein so RNA interference could be used to attack viruses that are resistant to all of the current inhibitors.” It is very likely that HIV would rapidly develop resistance to individual siRNAs because RNA interference is so sequence-specific, he adds. “So the next step will be to determine if different siRNAs can be expressed in the same cell since it will be harder for the virus to become resistant to multiple individuals simultaneously.”
People who did not nap did worse in the evening than the morning. “It’s like playing a piano piece continuously”, says Mednick. “You get worse as you get more tired.” By contrast, those who had a nap that included slow wave sleep retained good performance all day although they still did not learn. For that, explains Mednick, “a full cycle of slow wave and REM sleep was needed. Then their short daytime sleep improved learning as much as a full night’s sleep.” Siegel’s scepticism about the memory consolidation theory is not lessened by this new study. “I suspect that the people who had napped did better in the evening test simply because they were less sleepy”, he suggests. This was unlikely to be the case, counters Mednick, because when participants were tested in one visual quadrant and then retested later in the contralateral quadrant, both the deterioration in “non-nappers” and the improvement in “nappers” disappeared. Thus, she concludes, “our results cannot be explained by fatigue or otherwise of the whole person”.
Roxanne Nelson Jane Bradbury
2214
THE LANCET • Vol 361 • June 28, 2003 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet