Abstract: A transcribed non-naturally occuring RNA molecule comprising a desired RNA molecule, wherein the 3' region of the RNA is able to base-pair with at least 8 bases at the 5' terminus of the same RNA molecule.

Abstract: Human fetal neuro-derived cell lines are implanted into host tissues. The methods allow for treatment of a variety of neurological disorders and other diseases. A preferred cell line is SVG.

Abstract: A method of causing production and secretion into the bloodsream of a human patient of a biologically active enzyme for which the human patient suffers a deficiency; the method involves introducing into the human patient donor bone marrow stromal cells which have been transfected with a gene encoding the enzyme, so that the introduced cells can adhere to a bone cavity surface of the patient and produce and secrete the active enzyme.

Abstract: Novel capped oligonucleotides useful in treatment of influenza infection. A synthetically derived 67-nucleotide RNA substrate, containing a ?.sup.32 P! labeled cap-1 structure was used to analyze parameters of influenza virus endonuclease activity. This substrate was specifically cleaved by the influenza virus polymerase to yield a single capped 11-nucleotide fragment capable of directly priming transcription. An analysis of systematic truncations of this RNA substrate in cleavage, elongation, and binding reactions demonstrated that the minimum chain length required for cleavage was one nucleotide past the cleavage site. In contrast, the minimum chain length required for priming activity was found to be 9 nucleotides, while a chain length of at least 4 nucleotides was required for efficient binding.

Abstract: High titre helper-free recombinant retrovirus are produced by (a) growing a transfected host cell, produced by transfecting a eukaryotic host cell with a recombinant vector capable of stable episomal maintenance in the host cell, in a medium under conditions whereby the recombinant vector is stably maintained as an episome in the transfected host cell and transcripts of said vector form, with retroviral gag, pol and env gene products, an infectious retrovirus; and (b) isolating from the medium helper-free infectious retrovirus formed in the transfected host cell. The recombinant vectors comprise (i) a retroviral construct comprising an exogenous gene; (ii) a eukaryotic origin of replication sequence providing a substrate for replicase activity capable of replicating the vector in the host cell; and, (iii) a copy control sequence providing a substrate for a copy control activity capable of maintaining the vector at a stable copy number in the host cell.

Abstract: An animal cell is co-transfected with both a recombinant DNA viral vector which bears a promoter, a recombinase gene and a poly(A) sequence and a recombinant DNA viral vector which bears two recombinase-recognizing sequences and which further bears an origin of replication, a promoter, a foreign gene and a poly(A) sequence, each of which is located between the two recombinase-recognizing sequences. Thereafter, in the co-transfected animal cell, a DNA fragment containing the origin of replication, promoter, foreign gene and poly(A) sequence is excised from the vector by the action of a recombinase expressed in the another vector. The DNA fragment forms a circular DNA molecule which autonomously replicates in the co-transfected animal cell due to the origin of replication, whereby the foreign gene is continuously expressed.

Abstract: The present invention generally relates to methods for treating a host by implanting genetically unrelated cells in the host. More particularly, the present invention provides human fetal neuro-derived cell lines, and methods of treating a host by implantation of these immortalized human fetal neuro-derived cells into the host.

Abstract: Avian diseases, particularly those which threaten birds early in life, are controlled by embryonal vaccination using oil emulsion vaccines. The site of inoculation is the albumin end of the egg via entry through the air cell end of the egg.

Abstract: The present invention relates to the use of tumor suppressor genes in combination with a DNA damaging agent or factor for use in killing cells, and in particular cancerous cells. A tumor suppressor gene, p53, was delivered via a recombinant adenovirus-mediated gene transfer both in vitro and in vivo, in combination with a chemotherapeutic agent. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into tumors subcutaneously, followed by intraperitoneal administration of a DNA damaging agent, cisplatin, induced massive apoptotic destruction of the tumors. The invention also provides for the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.

Abstract: Disclosed are methods of reducing neovascularization and of treating various disorders associated with neovascularization. These methods include administering to a tissue or subject a synthetic oligonucleotide specific for vascular endothelial growth factor nucleic acid effective in inhibiting the expression of vascular endothelial growth factor.

Abstract: The present invention relates to novel adenovirus vectors for use in gene therapy which are designed to prevent the generation of replication-competent adenovirus (RCA) during in vitro propagation and clinical use. The invention also provides methods for the production of the novel virus vectors. These vectors maximize safety for clinical applications in which adenovirus vectors are used to transfer genes into recipient cells for gene therapy.

Abstract: Viruses or cells are targeted for selective internalization into a target in vive. A molecule Specific for a receptor on the surface of the target cell is introduced onto the surface of the virus or cell. The modified virus or cell binds the receptor in vive and is internalized by the target cell. The method provides vectors for selective delivery of nucleic acids to specific cell types in vivo and a means to alter the tropism of an infectious agent.

Abstract: A variety of genetic constructs are disclosed that will find both in vitro and in vivo use in the area of tumor biology and cancer therapy. In particular, expression constructs are provided that contain a p16 encoding region and other regulatory elements necessary for the expression of a p16 transcript. One version of the expression construct is a replication-deficient adenoviral vector. Also provided are methods for the transformation of cell lines and the inhibition of cancer cell proliferation.

Abstract: A method for selectively killing nervous system and peripheral neoplastic cells is provided. Viral vectors are used to selectively express a cytochrome P450 gene in neoplastic cells, whose gene product targets the cells for selective killing, by rendering the cells sensitive to a chemotherapeutic agent.

Abstract: Methods for the enhancement of bone marrow stem cell engraftment are provided for use in transplantation therapy and ex vivo gene therapy of a mammal. The methods involve the transplantation of quiescent stem cells for transplantation therapy and quiescent transfected stem cells for ex vivo gene therapy.

Abstract: A DNA molecule encoding a secretable mature epidermal growth factor (EGF) polypeptide is delivered to a skin wound. The cells that take up the recombinant DNA construct express soluble EGF that is secreted into surrounding fluid. The presence of the EGF accelerates, by a statistically significant amount, the healing time of a wound treated in this manner.The DNA molecule can be a genetic construction that expresses an EGF encoding portion that differs from the naturally occurring EGF precursor gene in that the only coding region retained from the precursor gene is that of the mature EGF polypeptide. Amino-terminal EGF-like repeats and the carboxy-terminal hydrophobic sequence that anchors natural EGF to the cell membrane are not present in the genetic construction.

Abstract: This invention provides a method of alleviating chronic pain in humans. Viable, implantable cells are selected which release neuroactive substances that reduce chronic pain. The cells are cultured to improve their viability, and administered into a region of the central nervous system of a patient who is suffering from chronic pain. The cells continue to secrete the neuroactive substances within the patient without exogenous stimulation. Suitable implantable cells include adrenal medullary tissue cells, chromaffin cells or genetically engineered cells.

Abstract: The invention provides a recombinant viral vector comprising the DNA of, or corresponding to, at least a portion of the genome of an adenovirus, which portion is capable of infecting a hepatic cell; and a human VLDL receptor gene operatively linked to regulatory sequences directing its expression. The vector is capable of expressing the normal VLDL receptor gene product in hepatic cells in vivo or in vitro. This viral vector is useful in the treatment of metabolic disorders caused by the accumulation of LDL in plasma, such as familial hypercholesterolemia or familial combined hyperlipidemia.

Abstract: A method and apparatus for performing gene therapy treatment. The method comprises selecting a genetic vector, introducing a genetic material into the genetic vector, combining the modified genetic vector with an electronic pulse delivery buffer solution with cells from an organism, and performing electronic pulse delivery on the combination in a reaction chamber to produce transformed cells, and placing the transformed cells into an organism. The reaction chamber includes a main chamber having a first substantially flat face and which holds a combination of the genetic material, a plurality of cells from the organism and an electronic pulse delivery buffer solution. The reaction chamber also includes a first electrode which has a second substantially flat face which is disposed opposite to and proximate to the first substantially flat face. The first electrode is coupled to receive electronic pulses to perform electronic pulse delivery of the genetic material into at least some of the plurality of cells.

Abstract: This invention provides a method of enhancing the delivery of a nucleic acid into a cell, wherein a complex is formed comprising the nucleic acid, a cationic liposome, and a replication-deficient adenovirus, and the complex is administered to the cell to thereby enhance delivery of the nucleic acid into the cell. The method can be used to deliver the nucleic acid into a cell in a subject by administering the above complex into the subject.