Gene Therapeutics: Methods and Applications of Direct Gene Transfer

430 Pages·1994·20.47 MB·English

by  Jon A. Wolff, Joshua Lederberg (auth.), Jon A. Wolff (eds.)

GENE THERAPEUTICS
Methods and Applications of
Direct Gene Transfer
GENE THERAPEUTICS
Methods and Applications of
Direct Gene Transfer
JonA. Wolff
Editor
Foreword by James F. Crow
92 Illustrations with some color art
Birkhauser
Boston • Basel • Berlin
JonA. Wolff
University of Wisconsin Medical School
Departments of Pediatrics, Medical Genetics, and Neurology
Waisman Center, Room 607
1500 Highland Avenue
Madison, WI 53705-2208
USA
Library of Congress Cataloging-in-Publication Data
Gene therapeutics: methods and applications of direct gene transfer I Jon A. Wolff, editor; foreword
by James F. Crow.
p. cm.
Includes bibliographical references and index.
ISBN-13: 978-1-4684-6824-3 e-ISBN-13: 978-1-4684-6822-9
DOl: 10.1007/978-1-4684-6822-9
1. Gene therapy. I. Wolff, Jon A. (Jon Asher), 1956-
[DNLM: 1. Gene Therapy-methods. 2. Transfection-methods. QW 51 G3256 1993]
RBI55.8.G46 1993
616.042-dc20
DNLMlDLC 93-42919
for Library of Congress CIP
m®
Printed on acid-free paper. Birkhiiuser U(J?J
©1994 Birkhauser Boston
Softcover reprint of the hardcover 1s t edition 1994
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ISBN-13: 978-1-4684-6824-3
Camera-ready copy prepared by the editor and fonnatted using Aldus PageMake~
987654321
To my wife Katalin,
for her understanding and inspiration.
Contents
Foreword
James F. Crow .............................................................................................. xi
Preface
Jon A. Wolff ............................................................................................... xiii
Contributors .................................................................................................... xv
I BACKGROUND
A History of Gene Transfer and Therapy
Jon A. Wolff and Joshua Lederberg ............................................................... 3
Producing Mouse Genetic Models for Human Diseases
J. David McDonald ..................................................................................... 26
Post-Transcriptional Considerations of Gene Expression: Translation,
MRNA Stability, and Poly(A) Processing
Gary Brewer ................................................................................................ 40
Promoters, Enhancers, and Inducible Elements for Gene Therapy
Robert G. Whalen ........................................................................................ 60
II METHODS AND MECHANISMS
Possible Mechanisms of DNA Uptake in Skeletal Muscle
Martin E. Dowty and Jon A. Wolff .............................................................. 82
Receptor-Mediated Gene Delivery Employing Adenovirus-Polylysine-
DNA Complexes
David T. Curiel ............................................................................................ 99
viii Contents
Gene Transfer in Mammalian Cells Using Liposomes as Carriers
Arun Singhal and Leaf Huang ................................................................... 118
In Vivo Gene Therapy via Receptor-Mediated DNA Delivery
Henry C. Chiou, George L Spitalny, June R. Merwin,
and Mark A. Findeis .................................................................................. 143
Calcium Phosphate-Mediated DNA Transfection
Patricia L. Chang ...................................................................................... 157
Cellular Internalization of Oligodeoxynucleotides
LeonardM. Neckers .................................................................................. 180
Gene Transfer via Particle Bombardment: Applications of the Accell
Gene Gun
Ning-Sun Yang, Carolyn De Luna, and Liang Cheng ............................... 193
Electrically-Induced DNA Transfer Into Cells. Electrotransfection
In Vivo
Sergei I. Sukharev, Alexander V. Titomirov, and VadimA. Klenchin ......... 210
III APPLICATIONS
Pharmacokinetic Considerations in the Use of Genes as
Pharmaceuticals
Fred D. Ledley ........................................................................................... 235
Virus-Mediated Genetic Treatment of Rodent Gliomas
E. Antonio Chiocca, Julie K. Andersen, Yoshiaki Takamiya,
Robert L. Martuza, and Xandra O. Breakefield ........................................ 245
Gene Therapy for Adenosine Deaminase Deficiency and Malignant
Solid Tumors
Kenneth W. Culver and R. Michael Blaese ................................................ 263
Development of Herpes Simplex Virus Vectors for Gene Transfer to the
Central Nervous System
Joseph C. Glorioso, Neal A. DeLuca, William F. Goins,
and David J. Fink ...................................................................................... 281
Direct Gene Transfer and Catheter Based Gene Delivery Systems:
Applications to Cardiovascular Diseases and Malignancy
Gregory E. Plautz, Elizabeth G. Nabel, and Gary J. Nabel... ................... 303
Contents ix
Gene Therapy for Arthritis
Christopher H. Evans and Paul D. Robbins ............................................. 320
Gene Therapy: The Advent of Adenovirus
Leslie D. Stratford-Perricaudet and Michel Perricaudet .......................... 344
In Vivo Gene Transfer Into the Heart
Jeffrey M. Leiden and Eliav Barr .............................................................. 363
Receptor-Mediated Targeted Gene Delivery Using Asialoglycoprotein-
Polylysine Conjugates
Stephen Furs and George Y. Wu ................................................................ 382
Retroviral-Mediated Gene Transfer and Duchenne Muscular Dystrophy
Matthew G. Dunckley and George Dickson .............................................. 391
Keyword Index .............................................................................................. 411
Foreword
During the first half century of genetics, coinciding with the first half of this cen-
tury, geneticists dreamt of the repair of genetic disease by altering or replacing
defective genes. H. J. Muller wrote of the great advantages of mutations,
"nanoneedles" in his apt term, for delicately probing physiological and chemical
processes. In the same spirit, genes could be used to provide treatments of needle
point delicacy. Yet, during this period no realistic possibility appeared; it remained
but a dream.
The situation changed abruptly at the half century. Microbial genetics and its
offshoot, cell culture genetics, provided the route. Pneumococcus transformation
showed that exogenous DNA could become a permanent part of the genome; yet
attempts to reproduce this in animals produced a few tantalizing hints of success,
but mostly failures. Transduction, using a virus as mediator, offered a better op-
portunity. The fITSt reproducible in vivo gene therapy in a whole animal came in
1981. This was in Drosophila, with a transposable element as carrier. Flies were
"cured" of a mutant eye color by incorporation of the normal allele, and the effect
was transmissible, foreshadowing not only somatic, but germ line gene therapy.
At the same time, retroviruses carrying human genes were found to be ex-
tremely efficient in transferring their contents to the chromosomes of cultured cells.
The viruses were simply doing what comes naturally and, as Dunckley and Dickson
point out in this book, this activity seems not to be impaired by carrying all but the
largest genes. By this time it was apparent that gene therapy would be developed;
it was only a matter of time.
Gene therapy will be of greatest value, at least in the easily foreseeable future,
for specific monogenic diseases. These, of course, are a small fraction of genetic
disease, and a still smaller fraction of all disease. But it is an important fraction,
because many of these diseases cause severe lifetime impairments, miserable for
the person, distressing for the family, and expensive for society.
The technological advances that facilitate gene therapy will also lead to better
treatments of other kinds. And they will lead to diagnosis at successively earlier
ages, with corresponding ease of removing defective embryos. As with medicine
in general, prevention is better than cure. Ironically, as it becomes increasingly
effective, gene therapy may become of lesser importance. Ideally we would have
xii Foreword
one generation of treatment for those diseases already existing, followed by pre-
vention of new ones.
How useful will gene therapy be for complex, polygenic disease? This will be
much more difficult, although a high-resolution physical and linkage map will aid
in the discovery of the more important individual components. There are grounds
for optimism, as several articles in this volume attest.
For many monogenic diseases the time for gene therapy is here. Clinical
trials are underway. Ethical doubts have been properly raised, but are of decreas-
ing intensity as well thought-out protocols provide more predictable and safer re-
lief for drastic disease. The humanitarian value of eliminating Duchenne muscular
dystrophy, in my view, strongly outweighs any slippery-slope fears. I cheer the
day that all existing Duchenne disease genes become extinct and we have ways of
early detection of new mutations.
Practical applications of molecular biology have been slow in coming, sur-
prisingly slow, but they are making up for this by an explosive growth now. The
dream at the beginning of the century will become the reality at its end. How
different this fin de siecle is from the last, though perhaps not in spirit.
James F. Crow
Preface
The best theories are usually those that explain much in simple tenns. There is a
certain beauty to such ideas. Physicists in search of a "theory of everything," for
example, like to admire the aesthetic qualities of their theoretical constructs.
The reasoning behind gene therapy is attractive for this very reason. It is simple:
if a genetic disease is caused by a dysfunctioning gene, then the disease state can
be corrected by giving the patient the nonnal, functioning gene.
Although gene therapy was initially fonnulated to treat single gene defects, it
now holds promise for a wide range of disorders, including cancer, heart disease,
and degenerative neurologic disorders. Potentially, it could be a "treatment of ev-
erything," or at least of many things.
Initial attempts at gene therapy involved the genetic modification of cells in
culture, which were then transplanted back into the body. This is known as an
indirect, or ex vivo, approach. The focus of this book is the simpler, in vivo ap-
proach that involves the direct introduction of genes into the body without cell
transplantation.
The direct approach resembles conventional phannaceutical delivery meth-
ods and promises to be much less expensive than the indirect, ex vivo approaches.
There is a certain elegance to its simplicity.
Of course, patients care only for alleviation of their disease. They are con-
cerned with risk versus benefit ratios, not with the aesthetics of the theoretical
underpinnings of their treatment. Only the results of clinical trials will enable us to
judge the clinical value of direct gene therapeutics. However, the tremendous
progress reported in this book suggests that this approach has a very promising
future.
The book is divided into three sections. The first provides a scientific back-
ground for the concepts involved in gene therapy that include a history of previous
experiments, and the production of mouse genetic models. The basic tenets of
expression are explored in one chapter that addresses transcription and another
chapter that addresses the post-transcriptional elements of expression. The second
section covers the spectacular new methodologies and how these systems work.
The methods include naked DNA, oligonucleotides, calcium phosphate precipita-
tion, polylysine-complexes, adenovirus-polylysine DNA complexes, liposomes,
electroporation, and particle bombardment. The third section covers applications