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`* MOLECULAR MEDICINE TODAY
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`Muscle-based gene therapy
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`Genentech Exhibit 2044
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`Hepatitis E vaccine @ Traditional Chinese medicine yields
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`a kinase inhibitor for use in cancer and HIV ® Gene therapy
`for HER-2-related cancer ® MR microscopy: a new
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`window to the lungs D. Choi, St Louis, USA
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`T. Cox, Cambridge, UK
`K. Culver, Gaithersburg, USA
`K. Davies, Oxford, UK
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`MOLECULAR MEDICINE TODAY, APRIL 1996
`
`has synthesized over 100ofits own novellipid
`vectors for such applications. In comparative
`studies in animals using a single plasmid,
`Genzyme’s most promising lipids are obtaining
`100-fold better expression than DC-cholesterol,
`but because every cell typeis different, what
`works in the lung maynot be optimal elsewhere,
`qualifies Gail Maderis, Vice President and
`Business Manager at Genzyme.
`Asforusing the £7A tumor-suppressorgene
`against HER-2, based onthe in vitro and in vivo
`
`studies, ‘I think it's a very promising area’, says
`Ing-Ming Chiu, Professor of Medicine,
`Biochemistry and Molecular Genetics at the Ohio
`State University College of Medicine (Columbus,
`OH, USA). The HER-2 geneis an outstanding
`target, according to David Stern, Associate
`Professorof Pathology and Biology, Yale University
`School of Medicine (New Haven, CT, USA), but
`he cautionsthat the product ofthe gene is probably
`not acting alone to cause cancer, as there are three
`other very closely related receptortyrosine
`
`kinases, HERs1, 3 and 4,that have a variety of
`hormonalligands to muddy the waters. Determining
`whichofthe four HERproteins is active in a
`given canceris an areathat Stern and his col-
`leaguesare investigating, developing methodolo-
`gy to assess this from tumorbiopsy specimens. In
`the future, using such information, gene therapy
`treatment aimedat other proto-oncogenes may be
`expected to be extendedto other forms ofcancer.
`
`David Holzman
`
`MR microscopy: a new window
`to the lungs
`
`{poe
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`
`
`UniversityCenterforInVivoMicroscopy.
`
`
`
`
`
`ClinicalMRi
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`volunteer of temporarily speaking like Donald
`Duck,noill effects were noted.
`Within four months, the researchers plan
`to begin producingthefirst functional MRI
`imagesof the lung. To do this they may turn
`to hyperpolarized xenon, which produces
`distinct MRI signals depending on whether
`it is dissolved in the blood or mixed with air
`in the lungs. In the meantime, efforts are
`already under way to make both MR
`microscopy andlung imaging less cumbersome
`andless expensive,to facilitate their use in
`clinical practice.
`
`Karla Harby
`
`Copyright ©1996Elsevier Science Ltd. All rights reserved. 1357 - 4310/96/$15.00
`This material was copied
`at the NLM and may be
`Subject US Copyright Laws
`
`139
`
`In February, one of the few centres in the world
`that specializes in ultra-high-resolution magnetic
`resonance (MR) microscopy, Duke University
`Medical Center (Durham, NC, USA), prepared
`to initiate studies using these devices and
`hyperpolarized helium to observe lung histology
`in living, breathing animals.
`According to G. Allan Johnson, Director of
`the Center for In Vivo Microscopy(a National
`Resource designated by the US NationalInstitutes
`of Health), this developmentis the merging of
`twodistinct lines of scientific enquiry. Oneis the
`effort to create atlases of the microscopic anatomy
`of the small animals used for research. Thefirst
`atlas produced with MR microscopy,that of the
`mouse embryo,is already available on computer
`disk from the center*. A secondatlas — ofthe rat
`brain ~ is currently under development.
`The second project culminated in September
`1995, when Dukeresearchers producedthefirst
`clear image of a human lung using hyperpolarized
`helium.In contrast to the MR microscopyatlases,
`which require specially designed instruments,
`this study was performed with a standard clinical
`MRmachine.
`Unlike frozen-section histology, MR
`microscopy imagesrevealtissues without
`damaging them or harming the study subject.
`This has enabled Johnson’s group to examine
`structures that had never been seen before, such
`as the bat cochlea, which is too small and
`delicate to endure being cut with a knife. They
`can also view structures in three dimensions,
`rotating them on computerscreensat will, or
`zoomingin to explore detail.
`
`* For information about purchasing the CD
`atlas of the mouse embryo,please contact
`Dr Bradley R. Smith, Center for In Vivo
`Microscopy, Box 3302, Duke Medical Center,
`Durham, NC 27710, USA.
`
`mouseembryos,created
`
`
`KindlybytheDukeUniversityCenterforInVivoMicroscopy.project.
`
`
`
`
`
`
`Three-dimensionalMRimagesofaspartofthevisiblemouse
`
`The resolution of MR
`microscopy images is many
`orders of magnitude higher
`than that of ordinary
`clinical MR imaging (MRI).
`While a typical ‘high
`resolution’ MRI exam might
`use a 1 mm tissue slice with
`1 mm resolution in plane to
`create a | mm’voxel,
`
`Duke’s poorest resolutions using
`
`MRmicroscopy are 100 jm’, and
`
`many imagesare obtained at
`
`10 ym’, This meansthat while
`
`currentclinical MRI canlocate a
`
`tumor, MR microscopy might, in
`the future, reveal whether that
`
`tumoris malignant or benign.
`
`Becauseof the unique structure
`ofthe living lung, creating MR
`
`imagesof this organ has been a
`
`particular challenge. Conventional
`images are produced by probing
`
`the energy states induced in
`
`protons, since water is so
`abundantin living tissues.
`In the lung, however, wateris scarce, and
`good MRimageshavebeenvirtually
`impossible to obtain.
`For this reason, Johnson andcolleagues
`collaborated with Hunter Middleton and
`Will Happer(Princeton University, NJ, USA),
`whohadthe expertise to use spin-exchange
`optical pumping to produce quantities of
`hyperpolarized helium. They produced the
`first-ever imagesof a human lungby using
`a standard, but adjusted, MR machine, and
`by having the volunteer inhale
`hyperpolarized *helium. A nobelgas,
`helium is chemically and biologically inert
`and, apart from the embarrassmentfor the
`
`
`
`
`
`ofhumanlung,using*helium.KindlyprovidedbytheDuke
`
`
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`4
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