Chemistry: molecular biology and microbiology – Treatment of micro-organisms or enzymes with electrical or... – Modification of viruses
Patent
1994-06-21
1997-03-18
Crouch, Deborah
Chemistry: molecular biology and microbiology
Treatment of micro-organisms or enzymes with electrical or...
Modification of viruses
435373, 935 57, C12N 1500, C12N 500
Patent
active
056122063
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The invention concerns the field of gene therapy and more particularly relates to a method for genetically modifying bone marrow cells of primates, and to cells that produce recombinant retroviral vectors that can be used in such a method.
PRIOR ART
Introduction
Developments in the field of molecular biology have led to a better understanding of the genetic basis underlying the development of a large numbers of disorders. It is expected that the genes which are associated with the diseases that occur most frequently will have been identified, cloned and characterized before the end of this century.
So far, molecular genetics has contributed to medicine by the development of diagnostic tools and methods and the biotechnological production of pharmaceuticals. It may be expected, however, that it will also be possible to use the increasing knowledge of genetics for an essentially new therapeutic treatment, the so-called gene therapy. The purpose of gene therapy is to treat disorders by genetically modifying somatic cells of patients. The uses of gene therapy are not limited to hereditary disorders; the treatment of acquired diseases is also considered to be one of the possibilities. Although this field of study is still in a preliminary stage and must be developed, therapeutic possibilities are in the distance which can drastically improve medicine in the future (1-3).
An important cell type for gene therapy purposes is the so-called haemopoietic stem cell which is situated in the bone marrow and is the precursor cell of all circulating blood cells. This stem cell can also multiply itself without losing its differentiating ability. The underlying idea of a gene therapy directed to these cells is that gene transfer to (a limited number of) stem cells may already be sufficient to replace the entire blood-forming tissue with genetically modified cells for a lifetime (4). This would enable treatment not only of diseases that are caused by a (hereditary) defect of blood cells, but also of diseases that are based on the inability to make a certain protein: the modified blood (forming) system could be a constant source of the protein, which could do its work at the places where necessary. It is also possible, with the introduction of genetic material into the blood system, to obtain resistance against infectious agents or even to overcome a predisposition to chronic diseases, such as rheumatism or diabetes.
Finally, it can be noted that in the treatment of some diseases it is to be preferred or necessary that the gene transfer to stem cells is performed on bone marrow cell populations from which certain cell types have been removed. One could for instance consider the use of gene therapy in the treatment of leukemia, in which case there should not occur any gene transfer to the leukemic cells.
Retroviral Vectors
One of the conditions for the realization of such a bone marrow gene therapy protocol is a technique by which genes can be incorporated into the chromosomes of target cells, in such a manner that those genes are also passed on to the daughter cells and that the desired protein product is produced in those cells.
In the invention described here, for this purpose use is made of recombinant retroviruses that carry with them the genes to be introduced and are capable of delivering them in mammalian cells. They make use of the natural characteristic of retroviruses to integrate efficiently and stably into the genome of the infected cell, but cannot themselves cause any productive infection anymore because they are replication-defective and are not contaminated with wild-type viruses (5, 6).
The recombinant retroviruses which are used within the framework of the present invention are all based on murine leukemia viruses (MuLV; 7). For gene therapy in humans, use will be made of so-called amphotropic retroviruses which have a broad host-specificity and can infect primate cells, in addition to murine cells.
For the production of recombinant retroviruses, two elements are required: ge
REFERENCES:
van Beusechem et al (1990) J. Exp. Med. 172, 729-736.
Markowitz et al (1988) J. Virol. 62, 1120-1124.
Valerio Domenico
van Beusechem Victor W.
Crouch Deborah
IntroGene B.V.
LandOfFree
Retrovirus infecting primate bone marrow cells and harvesting bo does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Retrovirus infecting primate bone marrow cells and harvesting bo, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Retrovirus infecting primate bone marrow cells and harvesting bo will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1705495