Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing – Genetically modified micro-organism – cell – or virus
Patent
1997-11-13
2000-08-01
Guzo, David
Drug, bio-affecting and body treating compositions
Whole live micro-organism, cell, or virus containing
Genetically modified micro-organism, cell, or virus
424 936, 4353201, 536 234, 536 235, 536 241, A61K 4800, C12N 1586, C07H 2104
Patent
active
060963042
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
Chemical insecticides are an integral component of modem agriculture, and have afforded an effective means for reducing crop damage by controlling insect pests. However, chemical agents are under continuous scrutiny due to the potential for environmental contamination, selection of resistant populations of agronomic pests, and toxicity to non-target organisms such as beneficial insects, aquatic organisms, animals and man. As a result, alternative strategies for insect control are being sought that are effective and yet benign to non-target populations and the environment. One of these strategies comprises the use of microorganisms that are naturally occurring pathogens of target insect populations. However, many candidate entomopathogens that would be promising insect control agents lack the properties of classical chemical insecticides that farmers and others in agribusiness have grown accustomed to. For instance, insect-specific viruses from the family Baculoviridae possess several favorable attributes, including host-specificity and inert environmental properties, but lack the ability to rapidly control a target population before significant crop damage takes place. Fortunately, modern molecular biology provides the tools necessary to favorably modify many of these properties in order to satisfy the needs of modern agriculture.
Baculoviruses are viruses pathogenic to invertebrates, and are characterized by possession of a double-stranded, circular DNA genome ranging in size from 80 to 200 kilobases. Baculoviruses are divided into three subfamilies, including non-occluded baculoviruses (NOVs), granulosis viruses (GVs) and nuclear polyhedrosis viruses (NPVs). Examples of NOVs are Orcytes rhinoceros NOV and Helicoverpa zea NOV. Examples of GVs include Plutella xylostella GV, Cydia pomonella GV, Pieris brassicae GV, and Trichoplusia ni GV. Examples of NPVs include Autographa californica NPV, Spodoptera exigua NPV, Heliothis armigera NPV, Helicoverpa zea NPV, Spodoptera frugiperda NPV, Trichoplusia NPV, Mamestra brassicae NPV, Lymantria dispar NPV, Spodoptera litturalis NPV, Syngrapha facifera NPV, Choristoneura fumiferana NPV, Anticarsia gemmatalis NPV, and Heliothis virescens NPV.
Although certain GVs and NOVs have been carefully studied, NPVs are the most thoroughly characterized of the baculovirus subfamilies. The infection cycle of NPVs involves two types of virions. Following infection of insect cells, budded virions (BVs or extra cellular virus, ECV) are produced upon movement of nucleocapsids to the plasma membrane. These virions shed their nuclear-derived coat in the cytoplasm and bud through the cytoplasmic membrane into the hemocoel of the insect host. This process leads to systemic infection of the host insect. Later in the infection process, virions become occluded (occluded virions) within a protein matrix consisting substantially of the polyhedrin protein, thus forming polyhedrin inclusion bodies (PIBs or occlusion bodies, OBs). These inclusion bodies are the orally infectious form of the virus, and provide for horizontal transmission of the virus between insect hosts (1,2). Uninfected larvae feed on virus-contaminated substrates and ingest PIBs. The proteinaceous matrix is solubilized by the action of the basic pH of the insect midgut found in many lepidopterous larvae. The liberated virion nucleocapsids, containing the viral DNA genome, attach to and infect the epithelial cells of the larval midgut. Typically, the infected insect will continue to develop and consume plant material while the virus exponentially propagates within the host. Eventually, often after several weeks or longer have passed, the infected larvae will become filly involved and expire.
An attractive attribute of baculoviruses is their narrow host specificity. These viruses infect only arthropods, and possess relatively narrow host ranges even within a particular insect order. Host specificity has been examined by electron microscopy, DNA hybridization and recombinant DNA technology (3-5). Thes
REFERENCES:
patent: 5770192 (1998-06-01), Cayley et al.
Zhang et al., Gene, vol. 105, pp. 61-72, 1991.
E. I. Du Pont de Nemours and Company
Guzo David
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