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Am J Translational Res 1(3):259-266,2009
Original Article
Identification of PTCH1 Requirement for Influenza Virus Using Random
Homozygous Gene Perturbation
Wu-Bo Li, Jie Zhu, Brit Hart, Baoquan Sui, Ke Weng, Shaojing Chang, Rebecca Geiger, Montserrat Torremorell,
Alan Mileham, Christy Glaney, Martha A. Mellancamp, Limin Li, Michael Goldblatt, Michael S. Kinch
Functional Genetics, Inc. 708 Quince Orchard Road, Gaithersburg, MD 20878, USA; Genus plc, Hendersonville,
TN 37075, USA; Currently at Ralco Nutrition Inc, Marshall, MN
Received March 31, 2009; accepted April, 2009; available online April, 2009
Abstract: Influenza infection remains a leading cause of infectious disease-mediated morbidity and mortality.
Accumulating evidence indicates that most variants of seasonal and pandemic influenza have developed
resistance to conventional therapies. Such information has spawned new interest in identifying novel approaches
to target influenza. Our laboratories have been developing a new strategy of Host-Oriented Therapeutics, which
seeks to target host molecules in a safe and effective manner that prevents the virus from causing disease.
Using an improved discovery technology, Random Homozygous Gene Perturbation (RHGP), we identified the
PTCH1 protein as an essential host target that critically controls influenza virus infection. We further demonstrated
that targeted intervention against PTCH1 using antibodies or siRNA decreases influenza infection. Finally, we
demonstrated the involvement of PTCH1 in influenza infection outside of the laboratory by showing that genetic
variations of PTCH1 relate to decreased disease morbidity in the field. Altogether, these findings have important
implications for the development of novel, host-directed therapeutics to improve influenza disease management.
(AJTR903004).
Key Words: Influenza Virus, Random Homozygous Gene Perturbation (RHGP), PTCH1
Full Text PDF
Address all correspondence to:
Michael S Kinch
708 Quince Orchard Road
Gaithersburg, MD 20878 USA
mkinch@functional-genetics.com
Original Article
Identification of PTCH1 Requirement for Influenza Virus Using Random
Homozygous Gene Perturbation
Wu-Bo Li, Jie Zhu, Brit Hart, Baoquan Sui, Ke Weng, Shaojing Chang, Rebecca Geiger, Montserrat Torremorell,
Alan Mileham, Christy Glaney, Martha A. Mellancamp, Limin Li, Michael Goldblatt, Michael S. Kinch
Functional Genetics, Inc. 708 Quince Orchard Road, Gaithersburg, MD 20878, USA; Genus plc, Hendersonville,
TN 37075, USA; Currently at Ralco Nutrition Inc, Marshall, MN
Received March 31, 2009; accepted April, 2009; available online April, 2009
Abstract: Influenza infection remains a leading cause of infectious disease-mediated morbidity and mortality.
Accumulating evidence indicates that most variants of seasonal and pandemic influenza have developed
resistance to conventional therapies. Such information has spawned new interest in identifying novel approaches
to target influenza. Our laboratories have been developing a new strategy of Host-Oriented Therapeutics, which
seeks to target host molecules in a safe and effective manner that prevents the virus from causing disease.
Using an improved discovery technology, Random Homozygous Gene Perturbation (RHGP), we identified the
PTCH1 protein as an essential host target that critically controls influenza virus infection. We further demonstrated
that targeted intervention against PTCH1 using antibodies or siRNA decreases influenza infection. Finally, we
demonstrated the involvement of PTCH1 in influenza infection outside of the laboratory by showing that genetic
variations of PTCH1 relate to decreased disease morbidity in the field. Altogether, these findings have important
implications for the development of novel, host-directed therapeutics to improve influenza disease management.
(AJTR903004).
Key Words: Influenza Virus, Random Homozygous Gene Perturbation (RHGP), PTCH1
Full Text PDF
Address all correspondence to:
Michael S Kinch
708 Quince Orchard Road
Gaithersburg, MD 20878 USA
mkinch@functional-genetics.com
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