Chemistry: molecular biology and microbiology – Animal cell – per se ; composition thereof; process of... – Method of detaching cells – digesting tissue or establishing...
Patent
1996-03-22
2000-01-18
Campell, Bruce R.
Chemistry: molecular biology and microbiology
Animal cell, per se ; composition thereof; process of...
Method of detaching cells, digesting tissue or establishing...
435325, 800 20, 800 21, C12N 1500, C12N 500, A01K 6700
Patent
active
060157135
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to transgenic fish containing a modified insulin gene which has been altered to secrete humanized insulin. This invention further relates to the xenotransplantation of transgenic islets in the treatment of diabetes and to an improved method for mass isolation of fish islets.
RELATED APPLICATIONS
Pursuant to 35 U.S.C. .sctn..sctn. 119(e) and 120, this application claims priority from WO 96/32087, filed Mar. 22, 1996, which claims priority from U.S. Patent Application 08/417,866, filed Apr. 6, 1995, now abandoned.
BACKGROUND OF THE INVENTION
Diabetes mellitus is a disease resulting in significant morbidity and mortality. The total annual direct and indirect costs of diabetes in the Unites States exceeds $90 billion dollars. Insulin-dependent diabetes mellitus (IDDM), because it occurs in a younger population than non-IDDM, accounts for a disproportionate percentage of these costs. Although the acute manifestations of IDDM can be controlled with daily insulin injections, most patients eventually develop sequelae such as blindness, nephropathy, neuropathy, microangiopathy, and cardiovascular disease. Substantial evidence suggests that meticulous control of glycemia will prevent or minimize these sequelae.
A more physiological method of treating diabetes would be pancreas or islet transplantation. Whole or segmental pancreas transplantation has been performed successfully in man and some preliminary evidence suggests that this technique will prevent the sequelae of diabetes in man. However, pancreas transplantation is not trivial surgery; it poses problems with drainage for exocrine secretions and requires a lifetime of immunosuppressive therapy. On the other hand, islet transplantation has certain theoretical advantages--particularly related to the ease of surgery, the absence of extraneous exocrine tissue, and the cryopreservability of isolated islets. More importantly, islets are more amenable to immunoalteration. Various methods have been developed to prolong allograft survival without continuous immunosuppression in rats and mice. The ability to transplant islets without continuous immunosuppression may eventually prove absolutely necessary in man because many immunosuppressive drugs are somewhat toxic to islets.
Recent improvements in the methods of mass islet isolation and several recent clinical reports suggest that islet transplantation is on the verge of becoming a feasible treatment for IDDM. However, several obstacles exist. First, islets comprise only 2% of the human pancreas; yields from human "islet isolation" procedures are extremely variable and several human donor pancreases are often required to generate sufficient islets for a single transplant. Second, islet allograft rejection has proven difficult to manage using conventional methods and, unfortunately, the majority of islet allografts are quickly lost. Third, there are insufficient human donor pancreases available to treat the vast numbers of type I diabetic patients. Therefore, it seems likely that widespread implementation of islet transplantation would require the development of clinical islet xenotransplantation.
In response to this eventuality, many biomedical corporations are spending millions of dollars developing and patenting "bio-artificial pancreas" technologies (i.e., microencapsulation or macroencapsulation of islet tissue). The underlying concept behind these approaches is that the islet tissue is protected from the immune system by a membrane with pore sizes small enough to prevent immunocytes and antibodies from damaging the graft yet large enough for insulin, oxygen, glucose, and nutrients to pass freely.
During the past few years, several clinical islet transplantation centers have devoted extensive effort to develop experimental islet xenotransplantation models using large animals as donors. Most of these studies have centered on porcine, bovine, canine, or non-human primate islets. However, the pancreata in these species, like the human pancreas, are fibrous and do not read
REFERENCES:
patent: 5476779 (1995-12-01), Chen et al.
patent: 5545808 (1996-08-01), Hew et al.
Rokkones et al. Microinjection and expression of a mouse metallothionein human growth hormone fusion gene in fertilized salmonid eggs. J. Comp. Physiol. B, vol. 158, pp. 751-758, 1989.
Tiedge et al. Gene therapy of diabetes mellitus-aims, methods, and future prospects. Exp. and Clin. Biochem., vol. 103/suppl. 2, pp. 46-55, May 1995.
Noel et al. Prospects for genetic manipulation in diabetes. Diabetes Annual, vol. 10, pp. 65-84, 1996.
Chen et al. Trangenic fish: Ideal models for basic research and biotechnological applications. Zoological Studies, vol. 34, No. 4, pp. 215-234, Oct. 1995.
Chan et al. "Insulin and insulin-like growth factor genes in fishes and other primitive chordates" Biochemistry and molecular Biolocy of Fishes, 2, Hochachka P. and Mommesen T. (eds.) Amsterdam: Elsevier, 1993, pp. 407-17.
Furuchi et al. "A Radioimmunoassay Method for Determination of Fish Plasma Insulin" Bull Jap Soc. Sci Fish 46:1177-1181 (1980).
Gerber and Hare, "GABA in Peripheral Tissues: Presence and Actions in Endocrine Pancreatic Function" Brain Research Bulletin 5(Supp. 2):341-346 (1980).
Hobart et al. "Comparison of the nucleic acid sequence of anglerfish and mammalian insulin mRNA's from cloned CDNA's" Science 210: 1360-1363 (1980).
Iwata et al., "Feasibility of agarose microbeads with xenogeneic islets as a bioartificial pancreas" Journal of Biomedical Materials Research 28: 1003-1011 (1994).
Iwata et al., "Strategy for developing microbeads applicable to islet xenotransplantation into a spontaneous diabetic NOD mouse" Journal of Biomedical Materials Research 28: 1201-1207 (1994).
Kelly et al., "Experimental Diabetes Mellitus in a Teleost Fish. II. Roles of Insulin, Growth Hormone (GH), Insulin-Like Growth Factor-I, and Hepatic GH Receptors in Diabetic Growth Inhibition in the Goby, Gillichthys mairabilis" Endocrinology 132(6): 2696-2702 (1993).
Lanza et al., "A Simple Method for Transplanting Discordant Islets into Rats Using Alginate Gel Spheres" Transplantation 59:1485-9 (1995).
Mommesen and Plisetskaya, "Insulin in Fishes and Agnathans: History, Structure, and Metabolic Regulation" Rev. Aquacic Sci. 4:225-59 (1991).
Nguyen et al., "Characterization of the pancreatic hormones from the Brockmann body of the tilapia--implications for islet xenograft studies" Comp. Biochem. and Physiol IIIC(1): 33-44 (1995).
Patent and Foa, "Radioimmunoassay of Insulin in Fishes: Experiments in Vivo and in Vitro" Gen Comp Endocrinol 16:41-6 (1971).
Penman et al. "Factors affecting survival and integration following microinjection of novel DNA into rainbow trout eggs" Aquaculture 85: 35-50 (1990).
Pipeleers et al. "Glucose-induced insulin release depends on functional cooperation between islet cells" Proc. Natl. Acad. Sci. (USA) 79: 7322-7325 (1982).
Rahman and Maclean, "Production of transgenic tilapia (Oreochromis niloticus) by one-cell-stage microinjection" Aquaculture 105: 219-32 (1992).
Saiki et al., "Primer-Directed Enzymatic Amplification of DNA with a Thermostable DNA Polymerase" Science 239: 487-491 (1988).
Schrezenmeir et al., "Effect of Microencapsulation on Oxygen Distribution in Islets Organs" Transplantation 57: 1308-1314 (1994).
Schrezenmeir et al., "Long-Term Function of Single-Cell Preparations of Piscine Principal Islets in Hollow Fibers" Transplant Proc. 24:2941-2945 (1992).
Steiner et al. "Structure and Evolution of the Insulin Gene" Ann. Rev. Genet. 19:463-484 (1985).
Thorpe and Ince, "Plasma insulin levels in teleosts determined by a charcoal-separation radioimmunoassay technique" Gen Comp Endocrinol 30:332-339 1976.
Tilzey et al. "The development of a homologous teleost insulin radioimmunoassay and its use in the study of adrenaline on insulin secretion from isolated pancreatic islet tissue of the rainbow trout. Salmo gairdnerii (R.)" Comp Biochem Physiol. 81A:821-825 (1985).
Uraiwan and Doyle, "Replicate variance and the choice of selection procedure for tilapia (
Pohajdak Bill
Wright, Jr. James R.
Campell Bruce R.
Clark Deborah J. R.
Dalhousie University
Reiter Stephen E.
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