R.
Jude Samulski, PhD
Director,
Gene Therapy Center
Professor
of Pharmacology
PhD,
University of Florida
rjs@med.unc.edu
Dr.
Samulski's research focuses on the study of the dependent
parvovirus adeno-associated virus. AAV is the only known
DNA animal virus which requires co-infection by a second
unrelated virus in order to undergo productive infection.
The DNA tumor viruses, adenovirus and herpes simplex virus
provide the necessary helper functions for AAV. AAV not
only utilizes gene products from these tumor viruses,
but it interferes with their growth and with oncogenicity
of cells transformed by these viruses. In the absence
of a helper virus, AAV is able to integrate into host
cell DNA and maintain a latent infection. Superinfection
of these cells with a helper virus results in the rescue
and replication of the AAV genome. The ability of AAV
to integrate and maintain itself in host cells and subsequent
rescue and replication of its viral sequences is of considerable
interest. In some respects, this behavior is similar to
phenomena observed with bacterial transposons, yeast movable
genetic elements, Drosophila copia sequences, P elements,
and the RNA tumor viruses. For this reason AAV has recently
been described as a type of replicating transposon. Dr.
Samulski has cloned the AAV genome into the bacterial
plasmid pBR322 and demonstrated that this recombinant
clone is infectious when introduced into human cells co-infected
with a helper virus. This recombinant clone has provided
a manipulatable system for the analysis of mechanism(s)
involved in excision and integration of the adeno-associated
virus genome. Based on these observations, he has been
able to test AAV as a alternative viral vector for gene
delivery. The ability to generate non-pathogenic viral
vectors for current basic research have the long term
potential of serving as reagents for use in clinical settings.
He has established successful and long term gene expression
over a year, which directly addresses the issue of molecular
therapy required for genetic disorders. One of Dr. Samulski's
current goals of research is to continue to derive
delivery systems for use in gene therapy.
Recent Publications:
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- Wu Z, Asokan A, Grieger JC, Govindasamy
L, Agbandje-McKenna M, Samulski RJ.
Single amino acid changes can influence titer, heparin
binding, and tissue tropism in different adeno-associated
virus serotypes. Journal of Virology, 80(22)11393-7,
2006.
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- Asokan A, Hamra J, Govindasamy L, Agbandje-McKenna
M, Samulski RJ. Adeno-associated
virus type 2 contains an integrin alpha5beta1 binding
domain essential for viral cell entry. Journal
of Virology, 80(18):8961-9, 2006.
- Wu Z, Asokan A, Samulski RJ.
Adeno-associated virus serotypes: vector toolkit for human
gene therapy. Molecular Therapy, 14(3):316-27,
2006.
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McPhee SW, Janson CG,
Li C, Samulski RJ, Camp AS, Francis J, Shera D, Lioutermann
L, Feely M, Freese A, Leone P. Immune
responses to AAV in a phase I study for Canavan disease.
J Gene Medicine, 8(5):577-88, 2006.
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Hacker UT, Wingenfeld
L, Kofler DM, Schuhmann NK, Lutz S, Herold T, King
SB, Gerner FM, Perabo L, Rabinowitz J, McCarty DM,
Samulski RJ, Hallek M, Buning H. Adeno-associated
virus serotypes 1 to 5 mediated tumor cell directed
gene transfer and improvement of transduction efficiency.
J Gene Med, 7(11):1429-38, 2005.
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Chen S, Kapturczak
M, Loiler S, Zolotukhin S, Glushakova O, Madsen
K, Samulski RJ, Hauswirth W, Campbell-Thompson M,
Berns K, Flotte T, Atkinson M, Tisher C, Agarwal
A. Efficient
transduction of vascular endothelial cells with
recombinant adeno-associated virus serotype 1 and
5 vectors. Human Gene Therapy, 16(2):235-47,
2005.
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Ito H, Koefoed M, Tiyapatanaputi
P, Gromov K, Goater J, Carmouche J, Zhang X, Rubery
P, Rabinowitz J, Samulski RJ, Nakamura T, Soballe
K, O’Keefe R, Boyce B, Schwarz E. Remodeling
of cortical bone allografts mediated by adherent rAAV-RANKL
and VEGF gene therapy. Nature Medicine, 11(3):291-7,
2005.
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Chenuaud P, Larcher
T, Rabinowitz JE, Provost N, Joussemet B, Bujard H,
Samulski RJ, Favre D, Moullier P. Optimal
design of a single recombinant adeno-associated virus
derived from serotypes 1 and 2 to achieve more tightly
regulated transgene expression from nonhuman primate
muscle. Molecular Therapy, 9(3):410-418, 2004..
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Lehmann T, Wheeler
M, Froh M, Schwabe R, Bunzendahl H, Samulski RJ, Lemasters
J, Brenner D, Thurman RG. Effects of three suproxide
dismutase genes delivered with an adenovirus on graft
function after transplantation of fatty livers in
the rat. Transplantation, 76(1):28-37, 2003.
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Weber M, Rabinowitz
JE, Provost N, Conrath H, Folliot S, Briot D, Chérel
Y, Chenuaud P, Samulski RJ, Moullier P, Rolling F.
Recombinant
adeno-associated virus serotype 4 mediates unique
and exclusive long term transduction of retinal pigmented
epithelium (RPE) inrat, dog and nonhuman primate after
subretinal delivery. Molecular Therapy, 7(6):774-781,
2003
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Li
C, Hirsch M, Asokan A, Zeithaml B, Ma H, Kafri T, Samulski
RJ. AAV2 Capsid Specific Cytotoxic T lymphocytes only
Eliminate vector transduced Cells Co-expressing the
AAV2 Capsid in vivo. Journal of Virology, 2007.
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