Abstract: Compositions and methods are provided for gene delivery to the respiratory tract. In particular, compositions comprising a nebulized nucleic acid/stabilizing agent complex, and methods employing such complexes for pulmonary gene delivery, are provided. Such complexes are preferably sonic nebulized.

Abstract: A biodegradable, positively-charged aminoalkyl polyester polymer for the delivery of bioactive agents, such as DNA, RNA, oligonucleotides, proteins, peptides, and drugs is disclosed. Biologically active moieties, such as drugs, ligands, and the like, can be coupled to the free amino groups of the polymer.

Abstract: This invention provides improved devices and methods for long-term, stable expression of a biologically active molecule using a biocompatible capsule containing genetically engineered cells for the effective delivery of biologically active molecules to effect or enhance a biological function within a mammalian host. The novel capsules of this invention are biocompatible and are easily retrievable. This invention specifically provides improved methods and compositions which utilize cells transfected with recombinant DNA molecules comprising DNA sequences coding for biologically active molecules operatively linked to promoters that are not subject to down regulation in vivo upon implantation into a mammalian host. Furthermore, the methods of this invention allow for the long-term, stable and efficacious delivery of biologically active molecules from living cells to specific sites within a given mammal.

Abstract: A means for obtaining efficient introduction of exogenous genes into a patient, with long term expression of the gene, is disclosed. The gene, under control of an appropriate promoter for expression in a particular cell type, is encapsulated or dispersed with a biocompatible, preferably biodegradable polymeric matrix, where the gene is able to diffuse out of the matrix over an extended period of time, for example, a period of three to twelve months or longer. The matrix is preferably in the form of a microparticle such as a microsphere (where the gene is dispersed throughout a solid polymeric matrix) or microcapsule (gene is stored in the core of a polymeric shell), a film, an implant, or a coating on a device such as a stent. The size and composition of the polymeric device is selected to result in favorable release kinetics in tissue.

Abstract: The present invention provides an HSV having a genome from which, in the presence of the ICP4 gene product, a native immediate early gene is expressed with delayed kinetics, and an HSV having a genome with a mutation in each of the genes encoding ICP4, ICP27, and another HSV gene; preferably such HSV have one or more exogenous genes. The present invention further provides a method of expressing a polynucleotide within a cell comprising infecting the cell with such an HSV. Furthermore, the present invention provides a cell line having DNA encoding the HSV proteins ICP4, ICP27, and ICP0, and a method of producing an HSV vector by employing such a cell line.

Abstract: The present invention relates to variants of the human apolipoproteine A-I comprising a cystein in position 151, the corresponding nucleic acids and the vectors containing them. It also relates to pharmaceutical compositions comprising said elements and their utilization, particularly in genic therapy.

Abstract: Secretory gland cells, particularly pancreatic and salivary gland cells, are genetically altered to operatively incorporate a gene which expresses a protein which has a desired therapeutic effect on a mammalian subject. The expressed protein is secreted directly into the gastrointestinal tract and/or blood stream to obtain therapeutic blood levels of the protein thereby treating the patient in need of the protein. The transformed secretory gland cells provide long term therapeutic cures for diseases associated with a deficiency in a particular protein or which are amenable to treatment by overexpression of a protein.

Abstract: This invention relates compositions and methods for increasing the uptake of polynucleotides into cells. Specifically, the invention relates to vectors, targeting ligands, and polycationic agents. The polycationic agents are capable of (1) increasing the frequency of uptake of polynucleotides into a cell, (2) condensing polynucleotides; and (3) inhibiting serum and/or nuclease degradation of polynucleotides.

Abstract: The invention involves methods and products for oral gene therapy. Genes under the control of promoters are protectively contained in microparticles and delivered to cells in operative form, thereby obtaining noninvasive gene delivery for gene therapy.

Abstract: Recombinant adenoviruses comprising a heterologous DNA sequence coding for glial-derived neurotrophic growth factor (GDNF) are provided. The recombinant adenoviruses are useful in a method of expressing GDNF in a cell, wherein the cell is present in a mammal suffering from Parkinson's disease, comprising infecting said cell with a replication-defective recombinant adenovirus comprising a DNA sequence encoding GDNF operably linked to a promoter by administering the adenovirus into cells of the central nervous system. The recombinant adenoviruses of the invention are also useful in a method of treating Parkinson's disease comprising administering into cells of the central nervous system of a mammal suffering therefrom a replication defective recombinant adenovirus comprising ITRs, an encapsidation sequence and a DNA sequence encoding GDNF operably linked to a promoter, wherein the adenovirus E1 gene is non-functional and GDNF is expressed at a level that provides a therapeutic effect.

Abstract: Intestinal epithelial cells of a mammalian subject are genetically altered to operatively incorporate a gene which expresses a protein which has a desired therapeutic effect. Intestinal cell transformation is accomplished by administration of a formulation composed primarily of naked DNA, and is preferably administered orally. Oral or other intragastrointestinal routes of administration provide a simple method of administration, while the use of naked nucleic acid avoids the complications associated with use of viral vectors to accomplish gene therapy. The expressed protein is secreted directly into the gastrointestinal tract and/or blood stream to obtain therapeutic blood levels of the protein thereby treating the patient in need of the protein. The transformed intestinal epithelial cells provide short or long term therapeutic cures for diseases associated with a deficiency in a particular protein or which are amenable to treatment by overexpression of a protein.

Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of cardiovascular disease, including, but not limited to, atherosclerosis, ischemia/reperfusion, hypertension, restenosis, and arterial inflammation. Specifically, the present invention identifies and describes genes which are differentially expressed in cardiovascular disease states, relative to their expression in normal, or non-cardiovascular disease states, and/or in response to manipulations relevant to cardiovascular disease. Further, the present invention identifies and describes genes via the ability of their gene products to interact with gene products involved in cardiovascular disease. Still further, the present invention provides methods for the identification and therapeutic use of compounds as treatments of cardiovascular disease.

Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of cardiovascular disease, including, but not limited to, atherosclerosis, ischemia/reperfusion, hypertension, restenosis, and arterial inflammation. Specifically, the present invention identifies and describes genes which are differentially expressed in cardiovascular disease states, relative to their expression in normal, or non-cardiovascular disease states, and/or in response to manipulations relevant to cardiovascular disease. Further, the present invention identifies and describes genes via the ability of their gene products to interact with gene products involved in cardiovascular disease. Still further, the present invention provides methods for the identification and therapeutic use of compounds as treatments of cardiovascular disease.

Abstract: The present invention relates to a method for implanting producer cells into the mammalian brain. The producer cells are engineered with a retroviral based recombinant vector encoding a tumorcidal factor or susceptibility factor that confers on tumor cells sensitivity to chemotherapeutic or radiotherapeutic agents. Prior to transplantation into the mammalian brain, the producer cells are first cultured in vitro on a support matrix to increase the long-term viability of the transplanted cells and to provide long-term functional benefit.

Abstract: Cell compositions containing mononuclear phagocyte systems cells, and their use in cell therapy, e.g. adoptive immunotherapy, are disclosed.

Abstract: A novel targeted nucleotide sequence delivery and integration system is provided. The integration system employs nucleic acid constructs having a targeting sequence capable of binding AAV Rep and a heterologous nucleotide sequence arranged relative to the targeting sequence such that the targeting sequence is capable of directing the integration of the heterologous sequence into a target site in a recipient genome. The system further employs Rep expression products which provide integration functions effective to mediate the site-specific integration of the targeting sequence and the heterologous sequence into the recipient genome. Methods are described, whereby the nucleotide sequence integration system can deliver and efficiently integrate large nucleotide sequences into target sites in recipient cell genomes. Therapeutic methods are also provided, wherein the integration systems are used to insert various therapeutically relevant nucleotide sequences into selected cells from a subject.

Abstract: Nucleic acids are compacted, substantially without aggregation, to facilitate their uptake by target cells of an organism to which the compacted material is administered. The nucleic acids may achieve a clinical effect as a result of gene expression, hybridization to endogenous nucleic acids whose expression is undesired, or site-specific integration so that a target gene is replaced, modified or deleted. The targeting may be enhanced by means of a target cell-binding moiety. The nucleic acid is preferably compacted to a condensed state.

Abstract: Oligonucleotides containing unthylated CpG dinucleotides and therapeutic utilities based on their ability to stimulate an immune response in a subject are disclosed. Also disclosed are therapies for treating diseases associated with immune system activation that are initiated by unthylated CpG dinucleotides in a subject comprising administering to the subject oligonucleotides that do not contain unmethylated CpG sequences (i.e. methylated CpG sequences or no CpG sequence) to outcompete unmethylated CpG nucleic acids for binding. Further disclosed are methylated CpG containing dinucleotides for use antisense therapies or as in vivo hybridization probes, and immunoinhibitory oligonucleotides for use as antiviral therapeutics.

Abstract: Genes and gene products of Blk, a pro-apoptotic protein in the Bcl-2 gene family, are provided. Effector molecules that either increase or decrease Blk and thus promote or inhibit apoptosis are described. The Blk genes and proteins and effector molecules may be used to treat diseases that have unwanted cell proliferation used to promote cell growth.

Abstract: The present invention is directed to a leukocyte-specific gene Sp140 and its associated protein. Since it has structural analogies to other regulatory proteins and is localized in the nuclear body of certain cell types, Sp140 may be a transcription regulator involved in the body's interaction with viruses and in promyelocytic leukemia. The Sp140 gene can be used in gene therapy for treating certain viral diseases, autoimmune disorders and cancers, while the Sp140 protein may be useful as a diagnostic and prognostic marker in the analysis of certain autoimmune disorders.