Gene Therapy Methods

737 Pages·2002·14.425 MB·English

by  M. Ian Phillips

Preface
Gene therapy is less than ten years old and still very much in its infancy. The
first clinical gene therapy study was carried out in 1995 by Blaese and colleagues.
Although early results on clinical efficacy were disappointing, the logic of gene
therapy is irresistibly attractive. As science continues to evaluate the prospects for
gene therapy, so the clinical benefits have begun to be demonstrated. Early results
were hampered because of inadequate vectors for gene transfer. Most of the clinical
studies involved gene addition. However, gene therapy allows both correction and
replacement of defective genes. Ultimately, the goal is to have an in vivo somatic
gene therapy that can deal with not only immediate life-threatening diseases, such
as cancer and AIDS, but also chronic diseases that reduce the quality of life,
such as hypertension and inflammatory diseases. The basis for gene therapy is
understanding which genes are involved in diseased phenotypes and which vectors
are appropriate for providing therapeutic genes. The rapid progress in gene
discovery has been accelerated by the completion of the human genome project.
This book brings together, for the first time, methods in gene therapy that reflect
the development of scientifically grounded systems for delivering genes. DNA can
be engineered to carry a therapeutic gene in sufficient quantities for full-scale clin-
ical trials. The methods can be classified as either viral or nonviral. Viral vectors
are replication defective viruses with part of their coding sequences replaced by
the therapeutic gene. These viral vectors include retroviruses, adenovirus, adeno-
associated virus, herpes simplex viruS, papillomavirus, and lentivirus. Nonviral
vectors are simpler and easier to produce on the large scale. However, each has
its advantage. Viral vectors can be engineered to be expressed in specific tissue
and only under specific conditions. Nonviral vectors are less easy to control so
precisely. Some diseases need gene therapy for a rapid effect, such as killing off
tumor cells. Others need the presence of a stable, safe gene delivery system for
chronic lifetime diseases. The use of gene therapy could eliminate the need for
repeated administrations, improved therapeutic efficacy, and fewer side effects.
In hypertension, for example, one of the major problems is the lack of patient
compliance in taking current prescribed drugs that have to be administered once a
day. The prospect of prolonged effective control of blood pressure and the subse-
quent reduction in heart attacks, stroke, and end-stage renal disease are an exciting
possibility of the true benefits of gene therapy.
In this book we have brought together some of the leading researchers and
research methods in gene therapy. There are many ways to classify these chapters:
by disease, by the type of method, or the type of delivery system. We have chosen
xix
xx SDOHTEM NI YGOLOMYZNE
to classify them under the main type of delivery system being investigated. How-
ever, each chapter stands on its own, offering scientific insight and experience with
a particular approach. In some cases they cross the boundaries of these classifi-
cations. Although this is the first volume entitled "Gene Therapy Methods" for
the Methods in Enzymology series, the increasing number of new methods and the
progress of gene therapy will undoubtedly require more volumes in the future.
I wish to thank the authors for their contributions. I also wish to thank Ms. Gayle
Butters of the University of Florida, Department of Physiology and Functional
Genomics, for her excellent editorial assistance. My thanks also go to Shirley
Light of Academic Press for her encouragement to do this volume.
M. IAN SPILLIHP
Contributors to Volume 346
Article numbers are in parentheses following the names of contributors.
Affiliations listed are current.
ANDREW H. BAKER (10), Department of EARS J. BRANDEN (6), Center for
Medicine and Therapeutics, University BioTechnology, Department of BiD-
of Glasgow, Glasgow GI1 6NT, United sciences, Karolinska Institute, SE-141 57
Kingdom Huddinge, Sweden t
PARAMITA YAYHDAPOYDNAB (2), ,neGilaV XANDRA BREAKEFIELD (34), Molecu-
Inc., Newtown, Pennsylvania 18940 lar Neurogenetics Unit, Massachusetts
General Hospital, Charlestown, Massa-
ANDREA BANFI (9), Department of Molec-
chusetts 02129
ular Pharmacology, Stanford University
School of Medicine, CCSR 4215, Stan-
J. S. BROMBERG (12), Institute for Gene
ford, California 94305
Therapy and Molecular Medicine, Mount
Sinai School of Medicine, New ,kroY
CATHERINE BARJOT (13), Department of
New York 10029
Human Genetics, University of Michigan,
Ann Arbor, Michigan *90184
VLADIMIR BUDKER (7), Departments of Pe-
diatrics and Medical Genetics, University
ARTHUR L. BEAUDET (11), Department of
of Wisconsin, Madison, Wisconsin 53705
Human and Molecular Genetics, Baylor
College of Medicine, Houston, Texas MARK M. BURCIN (31), Cardiogene, 40699
03077 Erkrath, Germany
HELEN M. BEAU (9), Department of Molec- MASSlMO BUVOLI (8), Department of
ular Pharmacology, Stanford University
Molecular, Cellular, and Developmental
School of Medicine, CCSR 4215,
,ygoloiB University of ,odaroloC ,redluoB
Stanford, California 94305
Colorado 80309
E BOROS (12), Institute for Gene Therapy
and Molecular Medicine, Mount Sinai CHERYL A. CARLSON (16), Department
School of Medicine, New ,kroY New York of Medicine, Division of Medical Gene-
92001 tics, University of Washington, Seattle,
Washington 98195
O. BOYER (17), Laboratoire de Biologie et
Thgrapeutique des Pathologies Immuni- M. G. CASTRO (17), Molecular Medicine
taires, Universit~ Pierre et Marie Curie, and Gene Therapy Unit School of
HOpital de la Piti#-Salp~tri#re, 75651 Medicine, University of Manchester,
Paris Cedex ,31 France Manchester M13 9PT, United ~modgniK
*Current affiliation: UMR INRA 703, ENVN--Atlanpole La Chanterie, F-44307 Nantes Cedex 3,
France
t Current affiliation: Clinical Research Center, Karolinska Institute, S-141 86 Stockholm, Sweden
Current affiliation: Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles,
California 90048
xi
xii CONTRIBUTORS TO VOLUME 346
YERFFEJ S. NIALREBMAHC (13), Depart- YLREVEB L. DAVIDSON (25), Depart-
ment of Neurology, University of ments of Internal Medicine, Neurology,
Washington School of Medicine, Seattle, Physiology, and Biophysics, College of
Washington 98195 Medicine, University of lowa, Iowa ,ytiC
Iowa 52242
EILUJ CHAO (14), Department of Biochem-
istry and Molecular Biology, Medical
ELEHCIM DE AMLAP (29), Institute for Can-
University of South Carolina, Charleston,
cer Research and Treatment, Laboratory
South Carolina 29425
for Gene Transfer and Therapy, Univer-
EEL CHAO (14), Department of Biochem- sity of Torino Medical School 10060
istry and Molecular Biology, Medical Candiolo, Torino, Italy
University of South Carolina, Charleston,
South Carolina 29425 .Y DING (12), Institute for Gene Therapy and
Molecular Medicine, Mount Sinai School
EYK CHESNUT (24), Powell Gene Ther- of Medicine, New ,kroY New York 10029
apy Center, University of Florida,
Gainesville, Florida 32610 J. NIVEK EUHANOD (19), Institute of Molec-
ular Cardiobiology, Johns Hopkins Uni-
ATNAYAJ YOR YRUHDWOHC (2), Depart- versity School of Medicine, Baltimore,
ment of Medicine and Molecular Ge- Maryland 21205
netics, and Marion Bessin Liver Re-
NUY-NAIJ DONG (30), Department of Mi-
search Center, Albert Einstein College of
,ygoloiborc Medical University of South
Medicine, Bronx, New York 16401
Carolina, Charleston, South Carolina
ATIMAN YOR YRUHDWOHC (2), Department 29425
of Medicine and Molecular Genetics, and
GNEHSGNOD DUAN (20), Department of
Marion Bessin Liver Research ,retneC
Anatomy and Cell Biology, University of
Albert Einstein College of Medicine,
Iowa College of Medicine, Iowa City,
Bronx, New York 16401
Iowa 52242
YI CHU (15), Cardiovascular Division, FIONA M. DRALLE (27), Department of -DiB
University of lowa College of Medicine, chemistry, Oxford BioMedica (UK) Limi-
Iowa City, Iowa 52242
ted, Oxford OX4 4GA, United Kingdom
MARINEE K. L. CHUAH (33), Flanders NHOJ E TDRAHLEGNE (20), Department of
Interuniversity Institute of Biotechnol- Anatomy and Cell Biology, University of
ogy, Center for Transgene Technology Iowa College of Medicine, Iowa City,
and Gene Therapy, University of Leuven, Iowa 52242
B-3000 Leuven, Belgium
DIVAD B. FENSKE (3), Department of Bio-
DESIRE COLLEN (33), Flanders Interuni- chemistry and Molecular Biology, Uni-
versity Institute of Biotechnology, Cen- versity of British Columbia, ,revuocnaV
ter for Transgene Technology and Gene British Columbia, Canada V6T 1Z3
Therapy, University of Leuven, B-3000
YRRET FLOTTE (24), Powell Gene Ther-
Leuven, Belgium
apy Center, University of Florida,
Gainesville, Florida 32610
PIETER R. CULLIS (3), Department of
Biochemistry and Molecular Biology, AINOTNA IZNELLOF (26), IRCC, Institute for
University of British Columbia, Cancer Research and Treatment, Labo-
,revuocnaV British Columbia, Canada ratory for Gene Transfer and ,yparehT
V6T 1Z3, and Inex Pharmaceuticals Cor- University of Torino Medical School
poration, Burnaby, Canada V5J 5L8 10060 Candiolo, Torino, Italy
CONTRIBUTORS TO VOLUME 346 xiii
LENROC FRAEFEL (34), Institute of ,ygoloriV WILLIAM W. HAUSWIRTH (21), Depart-
University of Zurich, CH-8057 Zurich, ment of Ophthalmology and Powell Gene
Switzerland Therapy Center, College of Medicine,
NOSAJ J. FRITZ (21), Department of University of Florida, Gainesville,
Molecular Genetics and Microbiology, Florida 32610
College of Medicine, University of DONALD D. HEISTAD (15), Cardiovascular
Florida, Gainesville, Florida 32610 Division, University of Iowa College of
S. Fu (12), Institute for Gene Therapy and Medicine, Iowa City, Iowa 52242
Molecular Medicine, Mount Sinai School MIKKO O. HILTUNEN (18), University
of Medicine, New York, New York 10029 of Kuopio, A. L Virtanen Institute,
MARK R. GALLAGHER (23), Harvard/ FIN-70210 Kuopio, Finland
G~ngthon Joint Laboratory, Harvard WEHTTAM J. HUENTELMAN (32), De-
Institutes of Medicine, Boston, Mas- partment of Physiology and Functional
sachusetts 02115 Genomics, College of Medicine, Uni-
CRAIG H. GELBAND (32), Department of versity of Florida, Gainesville, Florida
Physiology, University of Florida College 32610
of Medicine and Functional Genomics, NEIL NOSHPESOJ (37), Division of Hema-
Gainesville, Florida 32610 ,ygolot University of ,notgnihsaW Seattle,
C. A. GERDES (l 7), Molecular Medicine and notgnihsaW 98195
Gene Therapy Unit School of Medicine, IMUFUSAY KANEDA (36), Division of Gene
University of Manchester, Manchester Therapy Science, Graduate School of
M13 9PT, United *modgniK Medicine, Osaka University, Suita ,ytiC
Osaka 565-0871, Japan
JILL GLASSPOOL-MALONE (4), Gene
Delivery Alliance, Inc., Rockville, Mary- MICHAEL J. KATOVICH (32), Department
land 20850 of Physiology and Functional Genomics,
College of Medicine, University of
JOHN T. GRAY (23), Harvard/G~n~thon
Florida, Gainesville, Florida 32610
Joint Laboratory, Harvard Institutes of
Medicine, Boston, Massachusetts 02115 NOBUFUMI KAWAI (22), Department of
Physiology, Jichi Medical School,
WALTER H. GiJNZBURG (35), Institute of -iV Kawachi, Tochigi 329-0498, Japan
,ygolor University of Veterinary Sciences,
SUSAN M. NAMSGN1K (27), Department of
A-1210 ,anneiV Austria
Biochemistry, Oxford BioMedica (UK)
Limited, Oxford 4XO 4GA, United
AKATUY HANAZONO (22), Division of Ge-
Kingdom
netic Therapeutics, Center for Molec-
ular Medicine, Jichi Medical School, D. KLATZMANN (17), Laboratoire de Bi-
Kawachi, Tochigi 329-0498, Japan ologie et Th~rapeutique des Patholo-
gies lmmunitaires, Universit~ Pierre et
KRISTINE HANSON (7), Departments of Pe- Marie Curie, CNRS, HOpital de la
diatrics and Medical Genetics, University
,ergirtgplaS-gitiP 75651 Paris Cedex ,31
of Wisconsin, Madison, Wisconsin 53705
France
DENNIS HARTIGAN-O'CONNOR (13), De- YSTEB T. KREN (2), Department of
partment of Neurology, University of Medicine, University of Minnesota Medi-
Washington School of Medicine, Seattle, cal School, Minneapolis, Minnesota
Washington 98195 55455
*Current affiliation: GlycArt Biotechnology AG, 8093 Zurich, Switzerland
xiv CONTRIBUTORS TO VOLUME 346
T. KU (12), Institute for Gene Therapy NAI MACLACHLAN (3), Protiva Biother-
and Molecular Medicine, Mount Sinai apeutics, Burnaby, British Columbia,
School of Medicine, New ,kroY New York Canada V5J 5L8
10029
TREBOR W. MALONE (4), Gene Delivery
AKIHIRO KUME (22), Division of Ge- Alliance, Inc., Rockville, Maryland 20850
netic Therapeutics, Center for Molec- ODRAUDE MARB,~N (19), Institute of
ular Medicine, Jichi Medical School Molecular Cardiobiology, The Johns
Kawachi, Tochigi 329-0498, Japan Hopkins University School of Medicine,
EILSEL A. DNAWNIEL (8), Department of Baltimore, Maryland 21205
Molecular, Cellular, and Developmental ENCA MARTIN-RENDON (27), Depart-
,ygoloiB University of ,odaroloC ,redluoB ment of Biochemistry, Oxford BioMedica
Colorado 80309 (UK) Limited, Oxford 4XO 4GA, United
Kingdom
ELLEHCIM K. LEPPO (19), Institute of
Molecular Cardiobiology, The Johns AIDYL C. MATHEWS (23), Harvard/
Hopkins University School of Medicine, Gdn(thon Joint Laboratory, Harvard
Baltimore, Maryland 21205 Institutes of Medicine, Boston, Mas-
sachusetts 02115
DERFLA S. LEWIN (21), Department of
Molecular Genetics and Microbiology, IHSAKAT MATSUSHITA (22), Division of
Powell Gene Therapy Center, College Genetic Therapeutics, Center for Molec-
of Medicine, University of Florida, ular Medicine, Jichi Medical School,
Gainesville, Florida 32610 Kawachi, Tochigi 329-0498, Japan
SALOHCIN D. MAZARAKIS (27), Depart-
ANDl~ LIEBER (16), Department of
ment of Biochemistry, Oxford BioMedica
Medicine, Division of Medical Genet-
(UK) Limited, Oxford OX4 4GA, United
ics, University of Washington, Seattle,
Kingdom
Washington 98195
PAUL B. McCRAY, .RJ (28), Departments
DEXI LIU (5), Department of Pharmaceu- of Pediatrics and Internal Medicine, Uni-
tical Sciences, University of Pittsburgh versity of Iowa, Iowa City, Iowa 52242
School of Pharmacy, Pittsburgh, Penn-
SOCAIRYK A. SUONAHPORTIM (27), De-
sylvania 15261
partment of Biochemistry, Oxford Bio-
FENG LIU (5), Department of Pharmaceu- Medica (UK) Limited, Oxford OX4 4GA,
tical Sciences, University of Pittsburgh United Kingdom
School of Pharmacy, Pittsburgh, Penn- IKAORIH MIZUKAMI (22), Division of Ge-
sylvania 16251 netic Therapeutics, Center for Molec-
ular Medicine, Jichi Medical School,
J.-MATTHIAS LOHR (35), Department of
Kawachi, Tochigi 329-0498, Japan
Molecular Gastroenterology, Medical
Clinic ,II University of Heidelberg, IHCIUYR ATIHSIROM (36), Division of Gene
D-6816 7 Mannheim, Germany Therapy Science, Graduate School of
Medicine, Osaka University, Suita City,
.P R. LOWENSTEIN (17), Molecular
Osaka 565-0871, Japan
Medicine and Gene Therapy Unit School
of Medicine, University of Manches- SALOHCIN MUZYCZKA (24), Powell Gene
ter, Manchester M13 9PT, United Therapy Center, University of Florida,
*modgniK Gainesville, Florida 32610
*Current affiliation: Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles,
California 90048
CONTRIBUTORS TO VOLUME 346 xv
LUIGI IN1DLAN (26, 29, 33), Institute for M. NAI SPILLIHP (1), Department of Phys-
Cancer Research and Treatment, Labo- iology and Functional Genomics, Col-
ratory for Gene Transfer and Therapy, lege of Medicine, University of Florida,
University of Torino Medical School, Gainesville, Florida 32610
10060 Candiolo, Torino, Italy
MARK POTTER (24), Powell Gene Ther-
NATHALIE NEYROUD (19), Institute of apy Center, University of Florida,
Molecular Cardiobiology, The Johns Gainesville, Florida 32610
Hopkins University School of Medicine, L. QIN (12), Institute for Gene Therapy and
Baltimore, Maryland 21205 Molecular Medicine, Mount Sinai School
of Medicine, New York, New York 10029
STUART A. NICKLIN (10), Department of
Medicine and Therapeutics, University PIPPA A. EFFILCDAR (27), Department of
of Glasgow, Glasgow Gll 6NT, United Biochemistry, Oxford BioMedica (UK)
Kingdom Limited, Oxford OX4 4GA, United King-
dom
AYUSTAT NOMOTO (22), Division of Ge-
netic Therapeutics, Center for Molec- NAHOM K. RAIZADA (32), Department of
ular Medicine, Jichi Medical School, Physiology and Functional Genomics,
Kawachi, Tochigi 329-0498, Japan College of Medicine, University of
Florida, Gainesville, Florida 32610
SEMAJ S. NORRIS (30), Department of
SILLYHP .Y REAVES (32), Department
Microbiology and Immunology, Medical
of Physiology, College of Medicine,
University of South Carolina, Charleston,
University of Florida, GainesviUe,
South Carolina 29425
Maryland 32610
n. YELDARB NUSS (19), Institute of Molec-
ASERET C. RITCHIE (20), Department of
ular Cardiobiology, The Johns Hop-
Anatomy and Cell Biology, University of
kins University School of Medicine,
Iowa College of Medicine, Iowa City,
Baltimore, Maryland 21205
Iowa 52242
IHSAKAT OKADA (22), Division of Ge-
NAHTANOJ B. ROHLL (27), Department of
netic Therapeutics, Center for Molec-
Biochemistry, Oxford BioMedica (UK)
ular Medicine, Jichi Medical School,
Limited, Oxford OX4 4GA, United King-
Kawachi, Tochigi 329-0498, Japan
dom
BERT W. O'MALLEY (31), Department
NOYMES RUBINCHIK (30), Department
of Molecular and Cellular Biology,
of Microbiology, Medical University of
Baylor College of Medicine, Houston,
South Carolina, Charleston, South Car-
Texas 77030
olina 29425
KEIYA OZAWA (22), Division of Ge- DIVAD W. LLESSUR (37), Division of Hema-
netic Therapeutics, Center for Molec-
,ygolot University of ,notgnihsaW Seattle,
ular Medicine, Jichi Medical School,
Washington 98195
Kawachi, Tochigi 329-0498, Japan
TREBOR SALLER (35), Bavarian Nordic,
LucIo PASTORE (11), Department of D-82152 Martinsried, Austria
Human and Molecular Genetics, Baylor
College of Medicine, Houston, Texas BRIAN SALMONS (35), Austrian Nordic,
*03077 A-1210 ,anneiV Austria
*Current affiliation: CEINGE-Biotecnologie Avanzate and Dipartimento di Biochima e Biotecnologie
Mediche, Universit~t degli Studi di Napoli "Federico II," 80131 Napoli, Italy
xvi CONTRIBUTORS TO VOLUME 346
INNAVOIG SALVATORI (13), Department of HARMUT STECHER (16), Department of
Human Genetics, University of ,nagihciM Medicine, Division of Medical Genetics,
Ann Arbor, Michigan *90184 University of Washington, Seattle,
Washington 98195
KURT SCHILLINGER (31), Department of
Molecular and Cellular Biology, Baylor DROFFILC J. STEER (2), Department of
College of Medicine, Houston, Texas Medicine, University of Minnesota Med-
03077 ical School, Minneapolis, Minnesota
55455
YRTIMD M. VOTEMHKAYAHS (16), Depart-
ment of Medicine, Division of Medical NEELLOC S. STEIN (25), College of
Genetics, University of Washington, Medicine, University of lowa, Iowa ,ytiC
Seattle, Washington 98195 Iowa 52242
KUNIKO SHIMAZAKI (22), Department DIRK S. REDREAWNIETS (16), Department
of Physiology, Center for Molecu- of Medicine, Division of Medical Ge-
lar Medicine, Jichi Medical School, netics, University of ,notgnihsaW Seattle,
Kawachi, Tochigi 329-0498, Japan Washington 98195
KCIRTAP L. SINN (28), Departments of Pedi- R. SUNG (12), Institute for Gene Therapy
atrics and Internal Medicine, Program ni and Molecular Medicine, Mount Sinai
Gene Therapy, College of Medicine, Uni- School of Medicine, New ,kroY New York
versity of Iowa, Iowa City, Iowa 52242 92001
C. I. EDVARD SMITH (6), Center for C. E. THOMAS (17), Molecular Medicine
BioTechnology, Department of Bio- and Gene Therapy Unit School of
sciences, Karolinska Institute, SE-141 57 Medicine, University of Manchester,
Huddinge, Sweden t Manchester M13 9PT, United Kingdom II
DRAHCIR O. SNYDER (23), Harvard/ KIYOTAKE TOBITA (22), Department of
G~n~thon Joint Laboratory, Division ,ygoloriV Jichi Medical School, Kawachi,
of Molecular Medicine, ehT Children's igihcoT 329-0498, Japan
Hospital, Department of Pediatrics, S. TONDEUR (17), Laboratoire de Biologie
Harvard Institutes of Medicine, Boston, et Th~rapeutique des Pathologies lmmu-
Massachusetts ~51120 nitaires, Universit~ Pierre et Marie ,eiruC
H~pital de al Piti~ Salp~tri~re 75651
GNUOY K. SONG (5), Department of
Paris Cedex ,31 France
Pharmaceutical Sciences, University
of Pittsburgh School of Pharmacy, GRANT EGDIRBORT (37), Division of Hema-
Pittsburgh, Pennsylvania 15261 § ,ygolot University of ,notgnihsaW Seattle,
Washington 98195
MATTHEW L. SPRINGER (9), Department
of Molecular Pharmacology, Stanford AIHPOS .Y TSAI (31), Department of Molec-
University School of Medicine, CCSR ular and Cellular Biology, Baylor College
4215, Stanford, California 94305 of Medicine, Houston, Texas 77030
*Current affiliation: Department of Immunology, Sigma-Tau S.EA., 00040 Pomezia, Italy
tCurrent affiliation: Clinical Research Center, Karolinska Institute, S-141 86 Stockholm, Sweden
tnerruC~: affiliation: Powell Gene Therapy Center, Department of Molecular Genetics and Micro-
biology, University of Florida, Gainesville, Florida 32610
§Current affiliation: Department of Pharmacology, University of Pittsburgh School of Medicine,
Pittsburgh, Pennsylvania 16251
tnerruCII affiliation: Department of Pediatrics and Genetics, Stanford University, Stanford, California
94305
CONTRIBUTORS TO VOLUME 346 xvii
MIKKO .P NENURUT (18), A. L Virtanen In- GNOLNAIJ WANG (38), Lineberger Com-
stitute, University of Kuopio, FIN-70210 prehensive Cancer Center, University of
Kuopio, Finland North Carolina at Chapel Hill Chapel
Hill, North Carolina *99572
P. UMANA (17), Molecular Medicine and
Gene Therapy Unit School of Medicine, MAS WANG (34), Molecular Neurogenet-
University of Manchester, Manchester ics Unit, Massachusetts General Hospi-
M13 9PT, United *modgniK tal Charlestown, Massachusetts 02129
D. ALAN WHITE (21), Department of Molec-
MASASHI URABE (22), Division of Ge-
ular Genetics and Microbiology, Col-
netic Therapeutics, Center for Molec-
lege of Medicine, University of Florida,
ular Medicine, Jichi Medical School
Gainesville, Florida 32610
Kawachi, Tochigi 329-0498, Japan
EVETS J. WHITE (10), Department of
YRREIHT EHCSSEIRDNEDNAV (33), Flan- Medicine and Therapeutics, University
ders lnteruniversity Institute of Biotech- of Glasgow, Glasgow Gll 6NT, United
,ygolon Center for Transgene ygolonhceT Kingdom
and Gene Therapy, University of Leuven, PILLIHP SMAILLIW (7), Departments of Pe-
B-3000 Leuven, Belgium diatrics and Medical Genetics, University
of Wisconsin, Madison, Wisconsin 53705
EGROEG SOLUOPOLISSAV (37), Division of
NOJ A. WOLFF (7), Departments of Pedi-
Hematology, University of ,notgnihsaW
atrics and Medical Genetics, University
Seattle, Washington 98195
of Wisconsin, Madison, Wisconsin 53705
T. SIKAREV (17), Molecular Medicine and ENIARROL M. WORK (10), Department of
Gene Therapy Unit School of Medicine, Medicine and Therapeutics, University
University of Manchester, Manchester of Glasgow, Glasgow Gll 6NT, United
M13 9PT, United Kingdom Kingdom
JEAN-MICHEL H. SOV (deceased) (38), ZIYING NAY (20), Department of Anatomy
Lineberger Comprehensive Cancer Cen- and Cell Biology, University of Iowa Col-
,ret Department of Biochemistry and Bio- lege of Medicine, Iowa City, Iowa 52242
physics, University of North Carolina at
GNAUGNAIX EY (31), Department of Molec-
Chapel Hill Chapel Hill North Carolina
ular and Cellular Biology, Baylor College
27599
of Medicine, Houston, Texas 77030
CINDY WANG (14), Departments of Bio- OPPES ALAUTTREH-XLY (18), Department
chemistry and Molecular Biology, Med- of Molecular Medicine, A. .I Virtanen In-
ical University of South Carolina, stitute, University of Kuopio, FIN-70210
Charleston, South Carolina 29425 ,oipouK Finland
NUHSOUG WANG (28), Departments of Pe- HPESOJ ZABNER (28), Departments of Pe-
diatrics and Internal Medicine, Program diatrics and Internal Medicine, Program
in Gene Therapy, College of Medicine, in Gene Therapy, College of Medicine,
University of Iowa, Iowa City, Iowa University of Iowa, Iowa City, Iowa
52242 t 24225
*Current affiliation: GlycArt Biotechnology AG, 8093 Zurich, Switzerland
t Current affiliation: Departments of Medicine and Genetics, Gene Therapy Program, Louisiana State
University Health Sciences Center, New Orleans, Louisiana 70112
*Current affiliation: Division of Hematology/Oncology, Children's Hospital Boston, Boston,
Massachusetts 02115
xviii CONTRIBUTORS TO VOLUME 346
GNEHSIUG ZHANG (5), Department of NAHSEH ZHOU (11), Cell and Gene Ther-
Pharmaceutical Sciences, University apy Center, Baylor College of Medicine,
of Pittsburgh School of Pharmacy, Houston, Texas 77030
Pittsburgh, Pennsylvania 16251
IEGRES NIHKUTOLOZ (24), Department of
GNEFOUG ZHANG (7), Departments of Pedi- Molecular Genetics and Microbiology,
atrics and Medical Genetics, University Powell Gene Therapy Center, University
of Wisconsin, Madison, Wisconsin 53705 of Florida, Gainesville, Florida 32610