Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1996-01-04
1998-11-03
Eisenschenk, Frank C.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
536 235, 536 2351, 536 2352, 536 245, A01N 4304, C07H 2104
Patent
active
058308776
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to methods for administering biologically active peptides to a mammalian host by the introduction thereto of one or more polynucleotides to operatively encode for the peptides, preferably by non-invasive means. It also relates to the administration of said polynucleotides to prevent and treat illnesses and loss of immune function associated with aging in mammals.
2. Description of Related Art
The direct introduction of a biologically active peptide or protein into the cells of a patient can have significant therapeutic value. However, this approach also has several drawbacks. Of primary concern is the risk of potential toxicities, particularly at dosages sufficient to produce a biological response to the peptide. From a practical perspective, there is also the problem of the cost associated with isolating and purifying or synthesizing the peptides. Moreover, the clinical impact of the peptides is also limited by their relatively short half-life in vivo which usually results from their degradation by any proteases present in the target tissue.
For these reasons, introduction of a protein into a patient by delivery of a gene which will express the protein in the patient/host is an intriguing alternative to administering the protein. However, to date the principal means for introduction of foreign genetic material into a host has involved the integration of the gene into the host genome by, for example, transforming the host's cells with a viral vector. Direct in vivo gene transfer into postnatal animals has also been reported using DNA encapsulated in liposomes including DNA entrapped in proteoliposomes containing viral envelope receptor proteins.
In 1984, work at the NIH was reported which showed that intrahepatic injection of naked, cloned plasmid DNA for squirrel hepatitis into squirrels produced both viral infection and the formation of antiviral antibodies in the squirrels (Seeger, et al, Proc.Nat'l.Acad.Sci USA, 81:5849-5852, 1984). Several years later, Felgner, et al., reported that they obtained expression of protein from "naked" polynucleotides (i.e., DNA or RNA not associated with liposomes or a viral expression vector) injected into skeletal muscle tissue (Felgner, et al., Science, 247:1465, 1990; see also, PCT application WO 90/11092). Feigner, et al. surmised that muscle cells efficiently take up and express polynucleotides because of the unique structure of muscle tissue, which is comprised of multinucleated cells, sarcoplasmic reticulum and a transverse tubular system which extends deep into the muscle cell.
Although it has been supposed that cells of other tissues may also be able to take up naked polynucleotides, expression in other tissues has only been identified to date when delivery of the expressed gene was via a delivery system, e.g., liposomal transformation of the cells. Indeed, other researchers have suggested that uptake and expression of naked polynucleotides in tissues other than skeletal muscle does not occur at detectable or biologically active levels (see, e.g., Stribling, et aL., aerosol delivery of a gene occurred with use of a liposomal delivery system but not with introduction of DNA alone!; and, Tang, et al., Nature, coupled to colloidal gold beads into the skin of mice did not elicit an immune response!).
Although generally effective for gene expression within muscle cells, injection of DNA or RNA into muscle tissue for long-term therapy requires use of repeated injections to offset loss of expression from gene degradation. This approach may not only be time-consuming and expensive, but may also be impractical due to inflammation caused at and near the site of injection. Such inflammation can cause muscle or other somatic cells into which nucleotides are introduced to be themselves targeted by an immune response (see, e.g., Example I) and can lead to severe myonecrosis. Further, intramuscular injection of DNA not only risks injury to muscle tissue, but that injury apparently also compromises th
REFERENCES:
patent: 5077054 (1991-12-01), Amkraut et al.
patent: 5580859 (1996-12-01), Felgner et al.
patent: 5589466 (1996-12-01), Felgner et al.
General Medical Company The Ultimate Delivery System: Lectro Patch Offers Large Molecule, 8 Day Drug Delivery, Jan., 1992.
Carson Dennis A.
Raz Eyal
Eisenschenk Frank C.
Nolan Patrick
The Regents of the University of California
LandOfFree
Method, compositions and devices for administration of naked pol does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method, compositions and devices for administration of naked pol, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method, compositions and devices for administration of naked pol will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-689272