Table Of ContentGene Delivery Systems
DRUGS AND THE PHARMACEUTICAL SCIENCES
A Series of Textbooks and Monographs
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Gene Delivery Systems
Yashwant V. Pathak
Percutaneous Absorption: Drugs, Cosmetics, Mechanisms, Methods
Nina Dragićević and Howard Maibach
Handbook of Pharmaceutical Granulation Technology
Dilip M. Parikh
Biotechnology: the Science, the Products, the Government, the Business
Ronald P. Evens
Filtration and Purification in the Biopharmaceutical Industry, Third Edition
Maik W. Jornitz
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Paul G. Pearson and Larry Wienkers
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Gene Delivery Systems
Development and Applications
Edited by
Yashwant V. Pathak
First edition published 2022
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Library of Congress Cataloging-in-Publication Data
[Insert LoC Data here when available]
ISBN: 978- 1- 032- 02550- 6 (hbk)
ISBN: 978- 1- 032- 02972- 6 (pbk)
ISBN: 978- 1- 003- 18606- 9 (ebk)
DOI: 10.1201/9781003186069
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To the loving memories of my parents and Dr. Keshav Baliram
Hedgewar, who gave proper direction to my life; to my beloved wife
Seema, who gave positive meaning; and to my son Sarvadaman, who
gave a golden lining to my life.
I would like to dedicate this book to the loving memories of Ma
Chamanlaljee, Ma Lakshmanraojee Bhide and Ma Madhujee Limaye,
who mentored me selflessly and helped me to become a good and
socially useful human being.
Yashwant V. Pathak
Contents
Preface.......................................................................................................................ix
About the Editor ........................................................................................................xi
List of Contributors .................................................................................................xiii
Chapter 1 Overview of Development of Gene Therapy ........................................1
Ofosua Adi- Dako, Doris Kumadoh, Yashwant V. Pathak and
Nana Kwame Gyamerah
Chapter 2 Understanding the Technologies Involved
in Gene Therapy ..................................................................................21
Manish P. Patel, Jayvadan K. Patel, Mukesh Patel
and Govind Vyas
Chapter 3 Gene Therapy and Gene Correction: Target, Progress and
Challenges to Treat Human Diseases ..................................................37
Manish P. Patel, Sagar A. Popat and Jayvadan K. Patel
Chapter 4 Clinical Applications of siRNA .........................................................65
Seth Kwabena Amponsah, Ismaila Adams
and Kwasi Agyei Bugyei
Chapter 5 Human Genomics Projects, Gene Therapy and
Precision Medicine .............................................................................77
Sakshi Thassu and Yashwant V. Pathak
Chapter 6 The Current State of Non- Viral Vector–Based mRNA
Medicine Using Various Nanotechnology Applications ....................89
Kshama Patel, Preetam Dasika and Yashwant V. Pathak
Chapter 7 RNA- Based Vaccines for Infectious Disease ....................................105
Deepa Dehari, Aiswarya Chaudhuri, Sanjay Singh,
and Ashish Kumar Agrawal
Chapter 8 Conditional Replication of Oncolytic Virus Based
on Detection of Oncogenic mRNA ...................................................129
Rakesh Sharma, Arvind Trivedi and Robert Moffatt
vii
viii Contents
Chapter 9 Unilateral Ex Vivo Gene Therapy by GDNF in
Neurodegenerative Diseases ..............................................................155
Sonia Barua and Yashwant V. Pathak
Chapter 10 Gene Therapy for Cancer Treatment: Recent Trends
and Clinical Evidence .......................................................................163
Manish P. Patel, Mansi S. Shah, Mansi N. Athalye
and Jayvadan K. Patel
Chapter 11 Gene Therapy for Retina and Eye Diseases ......................................181
Khushboo Faldu and Jigna Shah
Chapter 12 COVID- 19 Vaccine Development and Applications .........................197
Kavita Trimal and Kalpana Joshi
Chapter 13 In Vivo Gene Therapy: AAV2 Vectors ............................................223
Vandit Shah and Jigna Shah
Chapter 14 Gene Therapy for Acquired Tissue Damage: Scope,
Quality, Non- Clinical and Clinical Guidelines
of Gene Therapy Medical Products .................................................243
Rakesh Sharma, Robert Moffatt, Yuvraj Singh Negi
and Shashi Prabha Singh
Chapter 15 iMRI for Clinical Gene Therapy ......................................................285
Disha Patel, Khushboo Faldu and Jigna Shah
Index .......................................................................................................................295
Preface
Human gene therapy was in a conceptual stage in the 20th century, but come the 21st
century, it has become a reality. The recombinant adeno- associated virus (rAAV) has
become a major gene therapy vector and spawned a multibillion dollar industry. With
the advent of the COVID- 19 pandemic in the last two years, gene therapy has become
a great tool to treat new virus infections. Most of the COVID- 19 virus vaccines are
using messenger RNA (mRNA) technology as a treatment tool.
The possibilities of rAAV gene therapy are continuing to grow. In addition,
advances in structural biology provide easier access to the molecular details respon-
sible for cell entry and escape from neutralizing antibodies. This is helping investiga-
tors design increasingly sophisticated capsid modification schemes to improve rAAV
vector properties. Newer challenges are forthcoming in developing drug delivery
systems to deliver various gene- based treatment, including mRNA, small interfer-
ing RNA (siRNA) and other gene therapies for treatment of various diseases. These
treatments are providing incredible solutions, especially for the treatment of chronic
diseases, including cancers and infectious diseases.
There is a lot to be understood about the key molecular interactions of capsids with
host factors, and one would anticipate continuing feedback into vector design over
the coming years. There are also areas in which the salient molecular interactions
remain largely uncharacterized, such as cellular immune responses, and so prog-
ress in vector delivery now involves empirical mitigation strategies. It is important
to emphasize that identification of the most critical host factors for entry is recent,
their characterization is ongoing and exploitation of the emerging understanding for
improved vector delivery is only just starting.
In the recent pandemic, two companies used gene- based mRNA technology to
develop a vaccine for COVID- 19 and successfully administered millions of doses
around the world. Using mRNA as a medicine is a fundamentally different approach
than treating diseases with other drug classes. mRNA plays a fundamental role in
human biology. It is the set of instructions by which cells make proteins and send
them to various parts of the body. mRNA medicines take advantage of normal bio-
logical processes to express proteins and create a desired therapeutic effect. This
enables the potential treatment of a broad spectrum of diseases, many of which
cannot be addressed with current technologies.
Seven scientists in the United States and Britain who have come up with a revolu-
tionary gene therapy cure for a rare genetic form of childhood blindness won a 1 mil-
lion euro ($1.15 million) prize in 2018 from Portugal’s Champalimaud Foundation.
Their gene augmentation therapy involved the delivery of healthy genes using engi-
neered harmless viruses, described by the foundation as “an elegant solution.”
A significant boost to gene therapy research was given in 2020 with the Nobel
Prize in Chemistry given to Emmanuelle Charpentier of the Max Planck Unit for the
Science of Pathogens and Jennifer Doudna of the University of California, Berkeley,
for their discovery of the CRISPR/Cas9 genetic scissors that have revolutionized
genome editing.
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