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:
-
Yazici
C, Yanoso L, Xie C, Reynolds DG, Samulski RJ, Samulski
J, Yannariello-Brown J, Gertzman AA, Zhang X, Awad
HA, Schwarz EM. The effect of surface
demineralization of cortical bone allograft on the
properties of recombinant adeno-associated virus
coatings. Biomaterials. 2008 Oct; 29 ( 28 ): 3882-7
. Epub 2008 Jun 30.
-
Li
W, Asokan A, Wu Z, Van Dyke T, DiPrimio N, Johnson
JS, Govindaswamy L, Agbandje-McKenna M, Leichtle
S, Redmond DE Jr, McCown TJ, Petermann KB, Sharpless
NE, Samulski RJ. Engineering and selection
of shuffled AAV genomes: a new strategy for producing
targeted biological nanoparticles. Mol Ther. 2008
Jul; 16 ( 7 ): 1252-60 . Epub 2008 May 20.
•
Lyon
AR, Sato M, Hajjar RJ, Samulski RJ, Harding SE. Gene
therapy: targeting the
myocardium. Heart. 2008 Jan; 94 (1):
89-99. Review.
-
Foti
S, Haberman RP, Samulski RJ, McCown TJ. Adeno-associated
virus-mediated expression and constitutive secretion
of NPY or NPY13-36 suppresses seizure activity in
vivo. Gene Ther. 2007 Nov; 14 ( 21 ): 1534-6 . Epub
2007 Aug 23.
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Maynor
BW, LaRue I, Hu Z, Rolland JP, Pandya A, Fu Q, Liu
J, Spontak RJ, Sheiko SS, Samulski RJ, Samulski
ET, DeSimone JM. Supramolecular nanomimetics:
replication of micelles, viruses, and other naturally
occurring nanoscale objects. Small. 2007 May; 3
( 5 ): 845-9 . No abstract available.
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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 Med. 2006 May;
8 ( 5 ): 577-88 .
•
Borrás
T, Xue W, Choi VW, Bartlett JS, Li G, Samulski RJ, Chisolm
SS. Mechanisms of AAV transduction in glaucoma-associated
human trabecular meshwork cells. J Gene Med. 2006 May;
8 ( 5 ): 589-602 .
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