Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Reexamination Certificate
2000-12-14
2002-10-29
Guzo, David (Department: 1636)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
C435S320100, C435S069700, C435S069800, C435S455000, C435S325000, C536S023100, C536S023200, C536S023400, C536S023500, C536S023700, C536S024100
Reexamination Certificate
active
06472176
ABSTRACT:
TECHNICAL FIELD OF THE INVENTION
The invention generally pertains to a polynucleotide that encodes a chimeric protein and related vectors, cells, and methods of expression thereof.
BACKGROUND OF THE INVENTION
The introduction of nucleotides, peptides, and small molecules into target cells and tissues is being developed as a therapeutic approach to a wide-range of diseases. The viability of this therapeutic approach has increased with the increased understanding of the molecular biology of cell division and differentiation, the identification of disease mechanisms, and the ability to develop high-throughput screens for agonists and antagonists of particular targets. A problem remains, however, which is inherent to all aspects of gene therapy. Namely, there continue to exist major hurdles for delivering therapeutic peptides and/or genes encoding therapeutic peptides to a sufficient number of target cells, such that the desired phenotypic response is elicited.
A wide variety of delivery methods has been proposed, including microinjection, scrape loading, electroporation, liposomes, bacterial toxins, and receptor-mediated endocytosis. Most of these methods, however, are inefficient and can cause appreciable cell death. Recently, it has been observed that the human immunodeficiency virus transcriptional activation protein (HIV TAT), the herpes simplex viral protein 22 (HSV VP22), and similar proteins possess the ability to enter numerous cell types when added exogenously to cells in vitro. Investigators also have discovered that these select proteins have the ability to carry nucleotides, small molecules, and/or other peptides which are bound to these proteins into target cells with high efficiency and, therefore, act as transport proteins.
Despite the potential of these transport proteins in aiding in the delivery of therapeutic agents, there still exist drawbacks, which limit the feasibility of this delivery approach. In particular, the preparation and purification of a desired therapeutic polypeptide comprising both a transport protein and a therapeutic agent can be both time-consuming and expensive. Furthermore, when these therapeutic polypeptides are administered in vivo to an organism, the therapeutic polypeptides are susceptible to proteolytic attack and can initiate an undesired, and potentially harmful, immune response by the treated organism. Consequently, delivery methods utilizing transport proteins can lead to less than desired stability in vivo and can actually be deleterious to the treated organism, if, indeed, an immune reaction is provoked.
Accordingly, there remains a need for an improved method of delivering therapeutic agents and other agents of interest in vivo to target cells. The invention seeks to provide such a method and agents for use therein. These and other objects and advantages of the invention will be apparent from the description of the invention provided herein.
BRIEF SUMMARY OF THE INVENTION
The invention provides a polynucleotide encoding a chimeric protein comprising an endoplasmic reticulum (ER) localization signal peptide, a transport moiety, and a moiety of interest, wherein the ER localization signal peptide, the transport moiety, and the moiety of interest are operably linked with each other. The invention further provides a vector comprising the polynucleotide, a cell comprising such a vector, and a method of expressing a protein comprising the transport moiety and the moiety of interest.
REFERENCES:
patent: 5580859 (1996-12-01), Felgner et al.
patent: 5801030 (1998-09-01), McVey et al.
patent: 5804604 (1998-09-01), Frankel et al.
patent: 5888762 (1999-03-01), Joliot et al.
patent: 6280989 (2001-08-01), Kapitonov et al.
patent: 6281413 (2001-08-01), Kramer et al.
patent: WO 99/16884 (1999-04-01), None
Aullo et al.,The EMBO Journal, 12 (3), 921-931 (Mar. 1993).
Bandara et al.,Nature Biotechnology, 15, 896-901 (Sep. 1997).
Chatelin et al.,Mechanisms of Development, 55, 111-117 (Apr. 1996).
Cress et al.,Journal of Virology, 68 (7), 4212-4219 (Jul. 1994).
Derer et al.,Journal of Molecular Medicine, 77, 609-613 (Aug. 1999).
Derossi et al.,Journal of Biological Chemistry, 269 (14), 10444-10450 (Apr. 1994).
Derossi et al.,Trends in Cell Biology, 8, 84-87 (Feb. 1998).
Elliott et al.,Gene Therapy, 6, 149-151 (Jan. 1999).
Fawell et al.,PNAS USA, 91 664-668 (Jan. 1994).
Fueyo et al.,Nature Medicine, 4 (6), 685-690 (Jun. 1998).
Goldstein et al.,Journal of Bacteriology, 172 (3), 1225-1231 (Mar. 1990).
Hall et al.,The Journal of Biological Chemistry, 265 (32), 19996-19999 (Nov. 1990).
Hawiger,Current Opinion in Immunology, 9, 189-194 (Apr. 1997).
He et al.,Nature, 373, 721-724 (Feb. 1995).
Inoue et al.,Annals of Microbiology, 133 A, 257-259 (Mar./Apr. 1982).
Izard et al.,Molecular Microbiology, 13 (5), 765-773 (Sep. 1994).
Joliot et al.,Current Biology, 8, 856-863 (Jul. 1998).
Joliot et al.,Development, 124, 1865-1875 (May 1997).
Ladunga,Current Opinion in Biotechnology, 11, 13-18 (Feb. 2000).
Mann et al.,The EMBO Journal, 10 (7), 1733-1739 (Jul. 1991).
Oess et al.,Gene Therapy, 7, 750-758 (May 2000).
Phelan et al.,Nature Biotechnology, 18, 440-443 (May 1998).
Prochiantz et al.,BioEssays, 17 (1), 39-44 (Jan. 1995).
Prochianz,Annals New York Academy of Sciences, 886, 179-179 (Nov. 1999).
Prochianz,Current Opinion in Neurobiology, 6, 629-634 (Oct. 1996).
Schwarze et al.,Trends in Cell Biology, 10, 290-295 (Jul. 2000).
Vivés et al.,The Journal of Biological Chemistry, 272 (25), 16010-16017 (Jun. 1997).
Yao et al.,Human Gene Therapy, 9, 1939-1950, (Sep. 1998).
Zheng et al.,Nature Neuroscience, 3 (6), 580-586 (Jun. 2000).
Bruder Joseph T.
Kovesdi Imre
GenVec, Inc.
Guzo David
Leydig , Voit & Mayer, Ltd.
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