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Home Gene Therapy Gene-transfer-using-transformed-neodetermined-embryonic-cells

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 Gene transfer using transformed, neodetermined, embryonic cells

Details
Inventors: Wagner, Thomas E.; Reed, Michael A.; Corn, Barbara J.;
Assignee: Ohio University Edison Animal Biotechnology Center (Athens, OH)
Primary Examiner: Weimar; Elizabeth C.
Assistant Examiner: Chambers; Jasemine C.
Attorney, Agent or Firm: Cooper; Iver P.

This invention is directed to a method for the preparation of carrier cells capable of delivering exogenous genetic material to a particular tissue of the body by means of embryonic cells competent to develop into that tissue, and essentially only that tissue, said cells bearing the exogenous genetic material. The preferred carrier cells are mesodermal cells of the yolk sac or embryonic forebrain or midbrain cells, and the desired genetic material is preferably introduced into the cells by in vitro transformation with an amphotrophic retroviral vector.

DETAILED DESCRIPTION This invention relates to the preparation of carrier cells capable of delivering genetic material to a particular tissue of the body by means of embryonic cells competent to develop into that tissue, and essentially only that tissue, said cells bearing the desired genetic material.
The preferred carrier cells are mesodermal cells of the yolk sac or embryonal forebrain or midbrain cells, and the desired genetic material is preferably introduced into the cells by transformation with an amphotrophic retroviral vector.
The yolk sac carrier cells are introduced intravenously.
Preferably, the carrier cells may be introduced into an immunocompetent host without provoking an immune response.
Mammalian development may be divided into three distinct stages: the zygote, from fertilization to cleavage; the embryo, from cleavage to the formation of all somites; and the fetus, from the formation of the last somite until birth.
This invention takes advantage of the unique properties of embryonic cells after their course of development is determined, but before they have lost immunoincompetency or the ability to proliferate rapidly.
An embryo begins with fertilization of an egg by a sperm.
The fertilized egg is called a zygote.
The unicellular zygote develops by successive mitotic divisions into a multicellular complex, the morula.
The cells of the morula move outward to form a blastula.
The daughter cells are called blastomeres, and are typically arrayed as a spherical layer, the blastoderm, surrounding a cavity, the blastocoele.
Gastrulation is the process by which the blastoderm differentiates into an ectoderm, a mesoderm, and an endoderm.
The ectoderm will develop into the skin and nervous system; the mesoderm, into the muscular, skeletal, circulatory and excretory systems; and the endoderm, into the digestive system.
For a number of organisms, "fate maps" have been ccnstructed which show the normal developmental fate of each part of the blastula.
In the early gastrula stage, the prospective potency of the neural area of the ectoderm is such that if cells are transplanted to another area, they can develop into not only epidermis, but also mesodermal or endodermal tissues



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