By James M. Wilson
ESI Special Topics,
November 2003
Citing URL - http://www.esi-topics.com/nhp/2003/november-03-JamesMWilson.html
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James M. Wilson
answers a few questions about this month's
new hot paper in the field of Microbiology.
From
•>>November 2003
Field:
Microbiology
Article Title: "Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy"
Authors: Gao,
GP;Alvira, MR;Wang, LL;Calcedo,
R;Johnston, J;Wilson, JM
Journal: PROC NAT ACAD SCI USA
Volume: 99
Page: 11854-11859
Year: SEP 3 2002
* Univ Penn, Inst Human Gene Therapy, Philadelphia, PA 19104 USA.
* Univ Penn, Inst Human Gene Therapy, Philadelphia, PA 19104 USA.
* Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
* Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA.
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 Why
do you think your paper is highly cited?
A critical path to the
success of gene therapy is the availability of gene-transfer
vehicles (i.e., vectors) that are safe and efficient. We have come
to learn that the vectors currently available have limitations.
One such vector system is based on the use of recombinant forms of
a group of parvoviruses called adeno-associated virus (AAV). Until
recently, virtually all studies of AAV biology were based on six
different isolates, five of which were identified as contaminants
in laboratory preparations of adenoviruses. The initial experience
with vectors based on these viruses has been mixed—in
 that the
level of gene transfer has been inadequate to confer therapeutic
efficacy in most applications even though transgene expression is
indeed stable and associated with little toxicity. We identified
two new isolates of AAV from nonhuman primates that were used to
create vectors which demonstrated substantially improved levels of
gene transfer in some target organs such as liver. If this
improved performance can be translated to humans it could open the
door for some therapeutic strategies that would not have been
feasible otherwise.
Does
it describe a new discovery or a new methodology that’s useful
to others?
Our study may be interesting to the scientific community for
several reasons. As described above, the newly discovered
viruses may form the basis for developing improved gene-transfer
vectors. In addition, the method used to recover the viruses
could be used to evaluate the frequency and distribution of
latent forms of AAV which could shed light on its biology in
primates.
Could you summarize the
significance of your paper in layman's terms?
An important step in the development of gene therapy is the
successful transfer of new genetic material into cells of the
recipient. This can be accomplished through the use of
attenuated viruses that have been engineered to contain a
therapeutic gene. The technical implementation of this strategy
has been difficult. One type of virus that has shown promise as
a gene-transfer vehicle (i.e., vector) is adeno-associated virus
(AAV). Our study describes the isolation of two new types of
AAVs that were used to create novel gene-transfer vehicles,
which show improved performance profiles in some applications
compared with previously described vectors.
How
did you become involved in this research?
My interest in gene therapy stems from my graduate studies at
the University of Michigan in the late 1970s and early 1980s
where I studied the genetic deficiency of an enzyme called HPRT
that causes the Lesch-Nyhan Syndrome. This disorder is
characterized by cerebral palsy, self mutilation, and neurologic
manifestations similar to what is seen in Huntington’s
disease. The goal of my work was to establish the molecular
basis of this disorder, which I did in a number of affected
subjects. It became clear, however, that the information gained
from my molecular pathogenesis studies was unlikely to lead to
new therapeutic outcomes for these individuals. Soon thereafter,
I refocused my efforts to the emerging new field of gene
therapy, which I have been pursuing for the last 20 years. My
approach has been to concentrate on the biology of gene
transfer, which has required developing competence in a number
of basic research areas including virology, immunology, and cell
biology.
James M. Wilson, M.D., Ph.D.
Institute for Human Gene Therapy
University of Pennsylvania
Wistar Institute
Philadelphia, PA, USA
Read comments from lead author Guang-Ping Gao
about this paper.
 This
paper was featured in Fast Breaking Papers - October
2003.
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ESI Special Topics,
November 2003
Citing URL - http://www.esi-topics.com/nhp/2003/november-03-JamesMWilson.html
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