- Email: [email protected]
Gene therapy for the head and neck
12
News & Comment
Two worms equal a human (by proteome) At the last count, the human genome was estimated to comprise 40 944 proteinencoding genes, about twice the number in worms. TMM editorial board member Kay Davies (University of Oxford, UK) made this claim at the autumn Genetics Society meeting (London, UK) based on statistics that define the proteome – the full set of proteins expressed by a human. This is considerably less than earlier estimates, which generally assumed a genome content of about 100 000 genes. The nematode Caenorhabditis elegans has over 18 000 genes, but only 959 adult cells, indicating that organism complexity is not predicted by gene number. According to the National Human Genome Research Institute (NHGRI) (USA) the existence of 38 000 genes, predicted by the genome sequence as it stands, has been confirmed experimentally. The NHGRI predicts that the complete human genome, including the precise number of genes, will be ready ahead of its 2003 schedule. (AR)
TRENDS in Molecular Medicine Vol.7 No.1 January 2001
easy to infect due to the presence of the human coxsackie and adenovirus receptor (hCAR). However, the group noted that expression of hCAR was most prevalent in undifferentiated dividing cells, particularly oropharyngeal tumor cells. This raises the prospect of adenoviral gene delivery to these tumor sites without affecting surrounding non-cancerous cells. Furthermore, such a system may prove useful in treating severe cellular dysplasia, a precancerous condition in which hCAR expression is maintained. Yarbrough commented, ‘theoretically, in people at high risk for cancer, adenoviral gene therapy would only infect the precancerous sites and leave the normal, well differentiated sites alone’. (AR)
Pufferfish genome sequencing
Black Death
Split-personality RANTES mutation A polymorphism in an immune system gene called RANTES (Regulated on Activation, Normal T Expressed and Secreted) has been shown to both increase the risk of HIV infection, but slow down the onset of AIDS. RANTES is a chemoattractant, which binds to the CCR5 receptor, and can thus inhibit HIV infection. The RANTES –403A polymorphism is believed to enact its split personality by increasing expression of the gene product, leading to increased inflammation, which permits easier entry of HIV in between cells; subsequently, the higher levels of RANTES protein result in fewer available receptors, slowing down progression to AIDS by 40%. (AR)
Gene therapy for the head and neck Wendel Yarbrough and colleagues (University of North Carolina at Chapel Hill, NC, USA) have made advances towards the treatment of head and neck cancer. 3-D cellculture models that imitate the real structure of head and neck epithelium were used as recipients of adenovirus-mediated gene delivery. Epithelial cells in a monolayer were
sarcoma skin tumours in AIDS patients. Research by John Pauk and colleagues at the Fred Hutchinson Cancer Center at the University of Washington in Seattle, contradicts previous suggestions that the virus is only transmitted through sexual intercourse. By studying over a hundred homosexual men in the Seattle area, the researchers found the virus in their saliva secretions and mouth swabs more often than in anal and genital samples. Up to 50% of HIV-infected people who catch HHV-8 develop Karposi’s sarcoma, which is rare in the non-infected population. The extensive saliva exchange involved in ‘deep kissing’ is likely to increase the risk of oral transmission of the virus. These results will create debate about including kissing warnings in future ‘safer sex’ campaigns. (JW)
Photograph courtesy of Ian Smith.
Following completion of the Drosophila genome sequence, and a full draft of the human genome, the Department of Energy’s Joint Genome Institute (CA, USA) has instigated a consortium to generate a complete genome sequence for the pufferfish Fugu rubripes. Fugu has a genome that carries the same fundamental genes and regulatory sequences as in humans, but is one-eighth of the size. This is due in part to the massive reduction in the size and number of introns. Comparative genomics using mouse sequence have proved extremely fruitful in decoding the human sequence, and it is hoped that researchers will elicit similarly valuable information from the pufferfish sequence. The consortium includes research groups from Los Alamos (CA), Pacific Northwest (WA) and Brookhaven (NY) National Laboratories, and Stanford University (CA). (AR)
Kissing and Karposi’s sarcoma A harmless kiss may spread the human herpesvirus 8 (HHV-8) that causes Karposi’s
The mediaeval pandemic called the Black Death has finally been scientifically identified as the plague. Black Death killed 17–28 million Europeans – up to one third of the total population – between the years 1347 and 1351, but identifying the culprit organism, and therefore the actual disease, has remained controversial. Variability in the mortality rates across different waves of Black Death led to the proposal of alternative etiologies, including anthrax and typhus. However, Didier Raoult and colleagues (Université de la Méditerranée, Marseille, France) have developed a sensitive, contamination-free technique called ‘suicide PCR’ to investigate the causative agent of the Black Death. The researchers isolated DNA from the dental pulp of pandemic victims whose skeletons were dug up from ancient mass graves around Montpellier in southern France. DNA was amplified from the bacterium Yersinia pestis in these victims, which indicates that the mediaeval Black Death was plague. This information may provide clues to understanding the recent reemergence of this highly infectious disease. (JW)
Adam Rutherford [email protected] Jonathan Weitzman [email protected]
http://tmm.trends.com 1471-4914/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.
News & Comment
Two worms equal a human (by proteome) At the last count, the human genome was estimated to comprise 40 944 proteinencoding genes, about twice the number in worms. TMM editorial board member Kay Davies (University of Oxford, UK) made this claim at the autumn Genetics Society meeting (London, UK) based on statistics that define the proteome – the full set of proteins expressed by a human. This is considerably less than earlier estimates, which generally assumed a genome content of about 100 000 genes. The nematode Caenorhabditis elegans has over 18 000 genes, but only 959 adult cells, indicating that organism complexity is not predicted by gene number. According to the National Human Genome Research Institute (NHGRI) (USA) the existence of 38 000 genes, predicted by the genome sequence as it stands, has been confirmed experimentally. The NHGRI predicts that the complete human genome, including the precise number of genes, will be ready ahead of its 2003 schedule. (AR)
TRENDS in Molecular Medicine Vol.7 No.1 January 2001
easy to infect due to the presence of the human coxsackie and adenovirus receptor (hCAR). However, the group noted that expression of hCAR was most prevalent in undifferentiated dividing cells, particularly oropharyngeal tumor cells. This raises the prospect of adenoviral gene delivery to these tumor sites without affecting surrounding non-cancerous cells. Furthermore, such a system may prove useful in treating severe cellular dysplasia, a precancerous condition in which hCAR expression is maintained. Yarbrough commented, ‘theoretically, in people at high risk for cancer, adenoviral gene therapy would only infect the precancerous sites and leave the normal, well differentiated sites alone’. (AR)
Pufferfish genome sequencing
Black Death
Split-personality RANTES mutation A polymorphism in an immune system gene called RANTES (Regulated on Activation, Normal T Expressed and Secreted) has been shown to both increase the risk of HIV infection, but slow down the onset of AIDS. RANTES is a chemoattractant, which binds to the CCR5 receptor, and can thus inhibit HIV infection. The RANTES –403A polymorphism is believed to enact its split personality by increasing expression of the gene product, leading to increased inflammation, which permits easier entry of HIV in between cells; subsequently, the higher levels of RANTES protein result in fewer available receptors, slowing down progression to AIDS by 40%. (AR)
Gene therapy for the head and neck Wendel Yarbrough and colleagues (University of North Carolina at Chapel Hill, NC, USA) have made advances towards the treatment of head and neck cancer. 3-D cellculture models that imitate the real structure of head and neck epithelium were used as recipients of adenovirus-mediated gene delivery. Epithelial cells in a monolayer were
sarcoma skin tumours in AIDS patients. Research by John Pauk and colleagues at the Fred Hutchinson Cancer Center at the University of Washington in Seattle, contradicts previous suggestions that the virus is only transmitted through sexual intercourse. By studying over a hundred homosexual men in the Seattle area, the researchers found the virus in their saliva secretions and mouth swabs more often than in anal and genital samples. Up to 50% of HIV-infected people who catch HHV-8 develop Karposi’s sarcoma, which is rare in the non-infected population. The extensive saliva exchange involved in ‘deep kissing’ is likely to increase the risk of oral transmission of the virus. These results will create debate about including kissing warnings in future ‘safer sex’ campaigns. (JW)
Photograph courtesy of Ian Smith.
Following completion of the Drosophila genome sequence, and a full draft of the human genome, the Department of Energy’s Joint Genome Institute (CA, USA) has instigated a consortium to generate a complete genome sequence for the pufferfish Fugu rubripes. Fugu has a genome that carries the same fundamental genes and regulatory sequences as in humans, but is one-eighth of the size. This is due in part to the massive reduction in the size and number of introns. Comparative genomics using mouse sequence have proved extremely fruitful in decoding the human sequence, and it is hoped that researchers will elicit similarly valuable information from the pufferfish sequence. The consortium includes research groups from Los Alamos (CA), Pacific Northwest (WA) and Brookhaven (NY) National Laboratories, and Stanford University (CA). (AR)
Kissing and Karposi’s sarcoma A harmless kiss may spread the human herpesvirus 8 (HHV-8) that causes Karposi’s
The mediaeval pandemic called the Black Death has finally been scientifically identified as the plague. Black Death killed 17–28 million Europeans – up to one third of the total population – between the years 1347 and 1351, but identifying the culprit organism, and therefore the actual disease, has remained controversial. Variability in the mortality rates across different waves of Black Death led to the proposal of alternative etiologies, including anthrax and typhus. However, Didier Raoult and colleagues (Université de la Méditerranée, Marseille, France) have developed a sensitive, contamination-free technique called ‘suicide PCR’ to investigate the causative agent of the Black Death. The researchers isolated DNA from the dental pulp of pandemic victims whose skeletons were dug up from ancient mass graves around Montpellier in southern France. DNA was amplified from the bacterium Yersinia pestis in these victims, which indicates that the mediaeval Black Death was plague. This information may provide clues to understanding the recent reemergence of this highly infectious disease. (JW)
Adam Rutherford [email protected] Jonathan Weitzman [email protected]
http://tmm.trends.com 1471-4914/01/$ – see front matter © 2001 Elsevier Science Ltd. All rights reserved.