Abstract: The present invention describes the preparation of unimolecular polymeric micelles (UPM) that bear a hydrophilic shell and a potentially ionizable and relatively hydrophobic core at a determined pH value. The core becomes electrostatically charged as the pH is changed. Such micelles can be made from either biodegradable or non-biodegradable polymers. Loaded drugs can be physically retained in the micelles when the pH of the surrounding medium favors interactions with the core. Upon a change in pH, modification in the ionization state of the core will decrease the interactions between the drug and the inner core and facilitate the release of the micellar contents.

Abstract: The invention provides a linear concatamer of at least two non-identical DNA sequences which, by virtue of third base redundancy of the genetic code of the codons, each encode the same polypeptide of at least 30 amino acids; wherein the concatamer comprises or consists of a nucleic acid sequence which codes for an oligomer of said polypeptides in a continuous reading frame. A single invariant cysteine codon may be added to one DNA sequence to encode a polypeptide derivative with a unique unpaired cysteine. The concatamer may be fused to one or more sequences encoding one or more antigens. The DNA sequences in the concatamer may encode the compliment C3 fragment C3d or an analogue thereof. The invention also provides an expression vector comprising the concatamer nucleic acid sequence and regulatory or other sequences for expression of any oligomeric polypeptide encoded thereby, as well as a host cell comprising the expression vector.

Abstract: The present invention relates to the delivery of desired compounds (e.g., nucleic acids) into cells using noncovalent delivery systems which include complexing nucleic acids, amphipathic binding agents, and amphiphiles.

Abstract: A family of isolated and purified proteins and nucleic acids are disclosed. Particularly, piwi family proteins and cDNAs encoding the same are disclosed. Recombinant host cells, recombinant nucleic acids, recombinant proteins and transgenic animals are also disclosed, along with methods of producing each. Isolated and purified antibodies to piwi family homologs, and methods of producing the same, are also disclosed. piwi family gene products are characterized as having activity in the growth, proliferation and self-renewing division of stem cells, and proliferation of primordial germ cells. Thus, therapeutic, screening, culturing and transgenic methods involving these activities are also disclosed.

Abstract: The invention relates to a novel CFTR gene regulatory element capable of increasing the activity of the CFTR gene promoter, and to nucleic acid constructs comprising the element together with the CFTR gene coding region. The element and constructs containing it are useful in gene therapy for treating cystic fibrosis.

Abstract: The present invention relates to a method for inhibiting a neurogenic inflammation caused or potentiated by an administration of viral vectors in gene therapy by administering to said mammal an antagonist that binds to a NK-1 receptor in an amount that is effective to inhibit said neurogenic inflammation.

Abstract: The present invention relates to an expression vector which expresses a malaria MSA1 peptide in combination with a signal peptide and anchor peptide in a host animal. The MSA1 peptide is combined with a signal peptide and anchor peptide for expression. Chimeric peptides being expressed with both signal peptides and anchor peptides were the most effective in eliciting an immunogenic response from a vaccinated host.

Abstract: A viral vector production system is provided which system comprises: (i) a viral genome comprising at least one first nucleotide sequence encoding a gene product capable of binding to and effecting the cleavage, directly or indirectly, of a second nucleotide sequence, or transcription product thereof, encoding a viral polypeptide required for the assembly of viral particles; (ii) a third nucleotide sequence encoding said viral polypeptide required for the assembly of the viral genome into viral particles, which third nucleotide sequence has a different nucleotide sequence to the second nucleotide sequence such that said third nucleotide sequence, or transcription product thereof, is resistant to cleavage directed by said gene product. The viral vector production system may be used to produce viral particles for use in treating or preventing viral infection.

Abstract: Novel cationic amphiphiles are provided that facilitate transport of biologically active (therapeutic) molecules into cells. The amphiphiles contain lipophilic groups derived from steroids, from mono or dialkylamines, or from alkyl or acyl groups; and cationic groups, protonatable at physiological pH, derived from amines, alkylamines or polyalkylamines. There are provided also therapeutic compositions prepared typically by contacting a dispersion of one or more cationic amphiphiles with the therapeutic molecules. Therapeutic molecules that can be delivered into cells according to the practice of the invention include DNA, RNA, and polypeptides. Representative uses of the therapeutic compositions of the invention include providing gene therapy, and delivery of antisense polynucleotides or biologically active polypeptides to cells. With respect to therapeutic compositions for gene therapy, the DNA is provided typically in the form of a plasmid for complexing with the cationic amphiphile.

Abstract: Provided are compositions and methods of use for insect cells comprising baculovirus encoding non-surface expressed proteins and peptides. The claimed invention particularly relates to compositions comprising insect cells containing baculovirus that express cytokines. Such compositions may be administered by, for example, direct intratumoral injection into tumors in mammals, resulting in tumor reduction or recission. Another aspect of the claimed invention concerns methods of promoting resistance to the reoccurence of tumors in mammals who have undergone such tumor recission. In a specific aspect of the claimed invention, the mammals are human subjects presenting with various forms of cancer.

Abstract: The present invention provides deleted adenovirus vectors. The inventive adenovirus vectors carry one or more deletions in the IVa2, 100K, polymerase and/or preterminal protein sequences of the adenovirus genome. The adenoviruses may additionally contain other deletions, mutations or other modifications as well. In particular preferred embodiments, the adenovirus genome is multiply deleted, i.e., carries two or more deletions therein. The deleted adenoviruses of the invention are “propagation-defective” in that the virus cannot replicate and produce new virions in the absence of complementing function(s). Preferred adenovirus vectors of the invention carry a heterologous nucleotide sequence encoding a protein or peptide associated with a metabolic disorder, more preferably a protein or peptide associated with a lysosomal or glycogen storage disease, most preferably, a lysosomal acid &agr;-glucosidase. Further provided are methods for producing the inventive deleted adenovirus vectors.

Abstract: An isolated DNA molecule encoding a Sox-9 gene which codes for the Sox-9 polypeptide. The human Sox-9 gene has been mapped to chromosome 17 in the same region as CMPD-1, the locus for Campomelic Dysplasia (CD). Sox-9 appears to have a role in mammalian skeletal development, and is used in the treatment of diseases involving bone or cartilage deficiency.

Abstract: Conventional liposomes which are used for transporting pharmaceutical active agents in eukaryotic cells or for lipofection can only be preserved for a limited period, are not acid-stable and require a number of set parameters in order to achieve satisfactory results. Less sensitive liposomes are therefore highly desirable. The inventive tetraetherlipid derivatives are very stable and are well suited to lipofection.

Abstract: A retroviral vector derived from a non-primate lentivirus genome comprising a deleted gag gene wherein the deletion in gag removes one or more nucleotides downstream of nucleotide 350 of the gag coding sequence.

Abstract: Presented are ways to address the problem of replication competent adenovirus in adenoviral production for use with, for example, gene therapy. Packaging cells having no overlapping sequences with a selected vector and are suited for large scale production of recombinant adenoviruses. A method of the invention produces adenovirus incapable of replicating. The method includes a primary cell containing a nucleic acid based on or derived from adenovirus and an isolated recombinant nucleic acid molecule for transfer into the primary cell. The isolated recombinant nucleic acid molecule is based on or derived from an adenovirus, and further has at least one functional encapsidating signal, and at least one functional Inverted Terminal Repeat. The isolated recombinant nucleic acid molecule lacks overlapping sequences with the nucleic acid of the cell.

Abstract: A genetically disabled mutant virus has a genome which is defective in respect of a selected gene that is essential for the production of infectious new virus particles, and which carries heterologous genetic material encoding an immunomodulatory protein such as GM-CSF, IL-2, or others, such that the mutant virus can infect normal host cells and cause expression of immunomodulatory protein, but the mutant virus cannot cause production of infectious new virus particles except when the virus infects recombinant complementing host cells expressing a gene that provides the function of the essential viral gene; the site of insertion of the heterologous genetic material encoding the immunomodulatory protein preferably being at the site of the defect in the selected essential viral gene. Uses include prophylactic and therapeutic use in generating an immune response in a subject treated therewith; use in the preparation of an immunogen such as a vaccine for use in tumor therapy; use in the in-vitro expansion of (e.g.

Abstract: The present invention is concerned with a vaccine for combating B. bronchiseptica infection in susceptible animals (such as dogs and swine), containing proteins or polypeptides typical of the fimbrial protein of B. bronchiseptica, or containing recombinant polynucleotides having as part thereof a polynucleotide coding for the protein or polypeptide, and also is concerned with the preparation of said proteins, polypeptides and polynucleotides.

Abstract: A novel adenovirus E1/E4 expressing packaging cell line is provided, which permits the generation of recombinant adenoviruses deleted in both gene regions. The E1/E4 deleted recombinant adenovirus is capable of expressing a selected transgene product in cells in vivo or in vitro. This recombinant virus is useful in the treatment of genetic disorders.

Abstract: A method of making a microparticle that contains DNA coding for a polypeptide is described in which a solvent extraction method is used and solvent extraction takes place at elevated temperature. Oral administration of the microparticle leads to its expression. DNA coding for an immunogen is for stimulating antibody formation in a recipient and DNA coding for a non-immunogenic polypeptide is for gene therapy applications. DNA is incorporated into the microparticle without destruction of its function.

Abstract: The present invention provides for improved methods of gene transfer, both in vitro and in vivo. By treating neoplastic cells with a DNA-damaging agent prior to transduction with a transgene, the expression of the transgene is improved up to about 3-fold over the expression seen in the absence of the DNA-damaging agent treatment. This effect is not dependent on the tumor cell type, the method of DNA transduction or type of DNA-damaging agent. The effect is most dramatic when the transduction is performed about 1-3 days following treatment with the DNA-damaging agent.