55 results about "Fibulin" patented technology

Adenovirus serotypes differ in their natural tropism. The adenovirus serotypes 2, 4, 5, and 7 all have a natural affiliation towards lung epithelia and other respiratory tissues. In contrast, serotypes 40 and 41 have a natural affiliation towards the gastrointestinal tract. The serotypes described, differ in at least capsid proteins (penton-base, hexon), proteins responsible for cell binding (fiber protein), and proteins involved in adenovirus replication. This difference in tropism and capsid protein among serotypes has led to the many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins.

The present invention relates to recombinant adenovirus serotype 5 (Ad5) vectors which harbor chimeric capsid proteins including substitutions of the corresponding regions from adenovirus serotypes having a lower seroprevalence relative to Ad5. In particular, the chimeric capsid includes modifications of both the adenoviral hexon and fiber proteins. The invention also provides methods for the treatment of diseases or disorders caused by infective agent(s) by administering the adenoviral vector(s) to a subject (e.g., a mammal, such as a human).

Bioscaffoldings formed of hydrogels that are crosslinked in situ in an infarcted region of the heart (myocardium) by a Michael's addition reaction or by a disulfide bond formed by an oxidative process are described. Each of the bioscaffoldings described includes hyaluronan as one of the hydrogel components and the other component is selected from collagen, collagen-laminin, poly-1-lysine, and fibrin. The bioscaffolding may further include an alginate component. The bioscaffoldings may have biofunctional groups such as angiogenic factors and stem cell homing factors bound to the collagen, collagen-laminin, poly-1-lysine, or fibrinogen hydrogel component. In particular, the biofunctional groups may be PR11, PR39, VEGF, bFGF, a polyarginine / DNA plasmid complex, or a DNA / polyethyleneimine (PEI) complex. Additionally, the hydrogel components may be injected into the infarct region along with stem cells and microspheres containing stem cell homing factors. The bioscaffolding may be formed on a stent or a cardiac medical device.

Disclosed is a method and test kit to diagnose tumorigenicity or the presence of tumor cells in a patient by detecting the level of FBLN-3 expression or biological activity in the patient. Also disclosed are methods to identify regulators of tumor cell growth, motility and / or invasion, by identifying regulators of FBLN-3 expression or activity. Methods to identify anti-angiogenic and pro-angiogenic agents are also described, wherein such factors regulate the expression and / or activity of FBLN-3. Finally, the present invention relates to therapeutic methods and reagents for the inhibition of tumor growth and development and / or for the inhibition or promotion of angiogenesis, using FBLN-3, homologues and analogs thereof, and agents that modulate the expression and / or activity of FBLN-3.

Modification of internal sites of the adenovirus fiber protein and hexon protein permit effective targeting of adenovirus vectors. Accessible sites to redirect adenovirus targeting were identified. The HVR5 loop of the hexon protein and the HI loop of the fiber protein (knob) were highly permissive for the insertion of foreign protein sequences, which apparently did not impact on the viability and productivity of corresponding viruses. Accessibility and functionality of the epitope strongly depend on the size of the neighboring spacers. Other results suggest that short targeting peptides can be effectively fused to the C-terminus of the fiber protein. In a specific embodiment, a series of adenovirus vectors modified at the HVR5 site, the fiber protein HI loop, or the fiber protein C-terminus to target urokinase-type plasminogen activator receptor bearing cells were prepared. Such vectors are particularly useful for targeting the vasculature, e.g., for gene therapy of cancers or cardiovascular conditions.

Adenovirus serotypes differ in their natural tropism. The adenovirus serotypes 2, 4, 5 and 7 all have a natural affiliation towards lung epithelia and other respiratory tissues. In contrast, serotypes 40 and 41 have a natural affiliation towards the gastrointestinal tract. The serotypes described differ in at least capsid proteins (penton-base, hexon), proteins responsible for cell binding (fiber protein), and proteins involved in adenovirus replication. This difference in tropism and capsid protein among serotypes has led to the many research efforts aimed at redirecting the adenovirus tropism by modification of the capsid proteins.

The invention provides an adenovirus or adenoviral vector characterized by comprising one or more particular nucleic acid sequences or one or more particular amino acid sequences, or portions thereof, pertaining to, for example, an adenoviral pIX protein, DNA polymerase protein, penton protein, hexon protein, and / or fiber protein.

The growth factor profile, connective tissue matrix constituents, and immunoprivileged status of urodele extracellular matrix (ECM) and accompanying cutaneous tissue, plus the presence of antimicrobial peptides there, render urodele-derived tissue an ideal source for biological scaffolds for xenotransplantation. In particular, a biological scaffold biomaterial can be obtained by a process that entails (A) obtaining a tissue sample from a urodele, where the tissue comprises ECM, inclusive of the basement membrane, and (B) subjecting the tissue sample to a decellularization process that maintains the structural and functional integrity of the extracellular matrix, by virtue of retaining its fibrous and non-fibrous proteins, glycoaminoglycans (GAGs) and proteoglycans, while removing sufficient cellular components of the sample to reduce or eliminate antigenicity and immunogenicity for xenograft purposes. The resultant urodele-derived biomaterial can be used to enhance restoration of skin homeostasis, to reduce the severity, duration and associated damage caused by post-surgical inflammation, and to promote progression of natural healing and regeneration processes. In addition, the biomaterial promotes the formation of remodeled tissue that is comparable in quality, function, and compliance to undamaged human tissue.

The invention provides an adenovirus or adenoviral vector characterized by comprising one or more particular nucleic acid sequences or one or more particular amino acid sequences, or portions thereof, pertaining to, for example, an adenoviral pIX protein, DNA polymerase protein, penton protein, hexon protein, and / or fiber protein.

Bioscaffoldings formed of hydrogels that are crosslinked in situ in an infarcted region of the heart (myocardium) by a Michael's addition reaction or by a disulfide bond formed by an oxidative process are described. Each of the bioscaffoldings described includes hyaluronan as one of the hydrogel components and the other component is selected from collagen, collagen-laminin, poly-l-lysine, and fibrin. The bioscaffolding may further include an alginate component. The bioscaffoldings may have biofunctional groups such as angiogenic factors and stem cell homing factors bound to the collagen, collagen-laminin, poly-l-lysine, or fibrinogen hydrogel component. In particular, the biofunctional groups may be PR11, PR39, VEGF, bFGF, a polyarginine / DNA plasmid complex, or a DNA / polyethyleneimine (PEI) complex. Additionally, the hydrogel components may be injected into the infarct region along with stem cells and microspheres containing stem cell homing factors. The bioscaffolding may be formed on a stent or a cardiac medical device.

The present invention relates to novel adenovirus strains with an improved seroprevalence in human. In one aspect, the present invention relates to isolated polypeptides of adenoviral capsid proteins such as hexon, penton and fiber protein and fragments thereof and polynucleotides encoding the same. Also provided is a vector comprising the isolated polynucleotide according to the invention and adenoviruses comprising the isolated polynucleotides or polypeptides according to the invention and a pharmaceutical composition comprising said vector, adenovirus, polypeptide and / or polynucleotide. The invention also relates to the use of the isolated polynucleotides, the isolated polypeptides, the vector, the adenoviruses and / or the pharmaceutical composition for the therapy or prophylaxis of a disease.

DNA sequences are identified that are useful in the diagnosis of gynaecological conditions such as endometriosis. Some of the sequences have a high identity with gene of known function such as Pim-2 oncogenes, IGFBP-5, ribosomal protein L41, propsaponin, fibulin-1, DLX5, 11β hydroxysteroid dehydrogenase type 2, SET, and RhoE. Methods for diagnosing or monitoring the progression of a gynaecological condition such as endometriosis may use primers directed to the DNA sequences identified herein.

The present invention provides a technique for conveniently and efficiently regenerating elastic fiber retaining a normal structure, and a technique enabling preparation of an artificial tissue comprising elastic fiber (for example, artificial skin, artificial blood vessels) that can be transplanted to humans. Specifically, the invention provides a method of producing elastic fiber, comprising culturing (for example, culturing in serum-free medium) cells having the capability of regenerating elastic fiber in the presence of DANCE and / or fibulin-4; artificial elastic fiber comprising DANCE and / or fibulin-4; an elastic fiber regenerating agent; a serum-free medium comprising DANCE and / or fibulin-4; and cells having the capability of regenerating elastic fiber, transfected with at least one of a DANCE expression vector, a fibulin-4 expression vector and a DANCE inducing factor expression vector, and the like.

A gene delivery vehicle having been provided with at least a tissue tropism for cells selected from the group of smooth muscle cells, endothelial cells, and / or liver cells. The tissue tropism is generally provided by a virus capsid, such as one comprising protein fragments from at least two different viruses, such as two different adenoviruses, including adenovirus of subgroup C or subgroup B (for example, adenovirus 16). The protein fragments can comprises a tissue tropism determining fragment of a fiber protein derived from a subgroup B adenovirus. Also, cells for producing such gene delivery vehicles and pharmaceutical compositions containing said gene delivery vehicles. Further, a method of delivering nucleic acid to cells such as smooth muscle cells and / or endothelial cells which involves administering to the cells an adenovirus capsid having proteins from at least two different adenoviruses and wherein at least a tissue tropism determining fragment of a fiber protein is derived from a subgroup B adenovirus. Particular construct are also disclosed.

The utility of adenovirus vectors (Ad) for gene therapy is restricted by their inability to selectively transduce disease-affected tissues. This limitation may be overcome by the derivation of vectors capable of interacting with receptors specifically expressed in the target tissue. Previous attempts to alter Ad tropism by genetic modification of the Ad fiber have had limited success due to structural conflicts between the fiber and the targeting ligand. The present invention presents a strategy to derive an Ad vector with enhanced targeting potential by a radical replacement of the fiber protein in the Ad capsid with a chimeric molecule containing a heterologous trimerization motif and a stabilized scFv ligand.

Disclosed is a mutant CAR-DI-binding adenovirus which has a genome comprising one or more mutations in sequences which encode the fiber protein knob domain wherein the mutation causes the encoded viral particle to have a significantly weakened binding affinity for CAR-DI relative to wild-type adenovirus. Such mutations may be in sequences which encode either the AB loop, or the HI loop of the fiber protein knob domain. Specific residues and mutations are described. Also disclosed is a method for generating a mutant adenovirus which is characterized by a receptor binding affinity or specificity which differs substantially from wild type.

The present invention involves the identification of mutations in various fibulin genes that contribute to age-related macular degeneration (AMD). Compositions and methods are provided to predict, diagnose and treat AMD using fibulin-1, fibulin-2, fibulin-4, fibulin-5 and fibulin-6 as targets.

The present invention relates to endothelial and smooth muscle cells genetically altered to express or over-express one or more cell adhesion factors. The invention further relates to cells genetically altered to express or over-express both cell proliferation growth factor(s) and cell adhesion factor(s). In addition, the present invention relates to nucleic acid constructs and nucleic acid construct systems that encode the cell adhesion and cell proliferation growth factors and that are used to transfect / transform the cells so that they can express the factors.

A gene delivery vehicle having been provided with at least a tissue tropism for cells selected from the group of smooth muscle cells, endothelial cells, and / or liver cells. The tissue tropism is generally provided by a virus capsid, such as one comprising protein fragments from at least two different viruses, such as two different adenoviruses, including adenovirus of subgroup C or subgroup B (for example, adenovirus 16). The protein fragments can comprise a tissue tropism-determining fragment of a fiber protein derived from a subgroup B adenovirus. Also, cells for producing such gene delivery vehicles and pharmaceutical compositions containing these gene delivery vehicles are provided. Further, a method is disclosed for delivering nucleic acid to cells such as smooth muscle cells and / or endothelial cells which involves administering to the cells an adenovirus capsid having proteins from at least two different adenoviruses and wherein at least a tissue tropism-determining fragment of a fiber protein is derived from a subgroup B adenovirus. Particular constructs are also disclosed.

The invention provides a replication-deficient serotype 28 adenoviral vector characterized by comprising a portion of a serotype 45 adenoviral hexon protein and / or a portion of a serotype 45 fiber protein in place of the endogenous serotype 28 hexon and / or fiber protein.

The invention provides an adenovirus or adenoviral vector characterized by comprising one or more particular nucleic acid sequences or one or more particular amino acid sequences, or portions thereof, pertaining to, for example, an adenoviral pIX protein, DNA polymerase protein, penton protein, hexon protein, and / or fiber protein.

Recombinant adenoviruses comprising modified fiber proteins which expand the tropism of the adenovirus in comparison to wild-type virus are disclosed. The modified fiber proteins described herein contain a peptide ligand for a cell surface binding site other than CAR comprising a 14 amino acid core sequence containing both fixed and variable amino acid residues. The invention includes isolated nucleic acid molecules encoding the modified adenovirus fiber proteins disclosed, as well as recombinant vectors and host cells containing said nucleic acid molecules. Methods of identifying peptide ligands that bind to cell binding sites other than CAR are included comprising screening a phage-display library of peptide ligands expressed within an adenovirus fiber knob context on CAR-negative cells. Recombinant adenoviruses of the present invention will increase the ability of an adenovirus to transduce important cell and tissue targets as part of a gene therapy / gene vaccination regime that have been shown to be refractory to adenoviral infection.

The invention relates to a high-expression prokaryotic cell expression system of non-sugar macromolecule protein containing a plurality of disulfide bonds or protein without important effect on the function affected by glycosyl, in particular to a prokaryotic cell expression system used for expressing a mutant type Plasminogen Activator (mt-PA) with bioactivity, which is characterized in that the mutant type Plasminogen Activator expression sequence (mt-PA) is constructed; an expression plasmid, which comprises an arabinose operon P promoter and the regulatory gene araC and is used for expressing the regulatory elements, is constructed, wherein, the expression plasmid contains the prokaryotic expression vector of the bacteria OmpA secreting signal peptides and the expression of mt-PA; an expression plasmid with isomerism enzyme DsbC or an expression plasmid without signal peptide DsbC is constructed; the expression plasmid of mt-PA and the DsbC or the expression plasmid without signal peptide DsbC are cotransformed to the trxB / gov mutated competent host strain; a secretion type human mt-PA engineering bacteria is constructed, which has the advantages of high level expression and biological activity.

A modified adenovirus capable of overcoming the problem of low level of coxsackie-adenovirus receptor (CAR) expression on tumor cells and methods of using such adenovirus are provided. The fiber protein of the adenovirus is modified by insertion or replacement so as to target the adenovirus to tumor cells, and the replication of the modified adenovirus is limited to tumor cells due to specific promoter control or mutations in E1a or E1b genes.

The invention is directed to novel combinations of liver specific enhancers and promoter elements for achieving persistent transgene expression in the liver. The liver specific enhancer elements may be derived from either the human serum albumin, prothrombin, α-1microglobulin or aldolase genes in single copies or in multimerized from linked to elements derived from the cytomegalovirus intermediate early (CMV), α-1-antitrypsin or albumin promoters. In a preferred embodiment of the invention, an adenoviral vector comprising a liver specific enhancer / promoter combination operably linked to a transgene is administered to recipient cells. In other embodiments of the invention, adeno-associated viral vectors, retroviral vectors, lentiviral vectors or a plasmid comprising the liver specific enhancer / promoter combination linked to a transgene is administered to recipient cells. Also within the scope of the invention are promoter elements derived from the human prothrombin gene and the β-fibrinogen gene.

The present invention relates to fibulin-3 protein and a pharmaceutical composition comprising the fibulin-3 protein as an active ingredient for inhibiting the growth of cancer stem cells. More particularly, in cancer stem cells separated from H460 and A549 cells, which are non-small-cell lung cancer cells, using ALDH1 activity as a marker, fibulin-3 induces the reductions of wnt / β-catenin, MMP2 and 7, which display characteristics of cancer stem cells, thereby decreasing the activated growth and penetration of the cancer stem cells. In addition, the purified fibulin-3 protein inhibits the growth of the non-small-cell lung cancer cell line A549, the breast cancer cell line MDA-MB231, and the cancer stem cell line active ALDH1. Therefore, fibulin-3 can be valuably used as an active ingredient of the pharmaceutical composition for inhibiting the growth of cancer stem cells.

A snake soluble fibrinous No.2 gene, carrier containing the gene, gene engineering xenological cell by the carrier, medicine for preparing albuminoid and treating embolic disease by the carrier are disclosed. It includes: separating snake venoms from fibrinolytical factor FII; screening and cloning fibrinolytical factor FII; expressing fibrinolytical factor FII yeast cell; purifying expressive product and determining fibrinolytical activity. It achieves low cost, high output and good quality.

Embodiments described herein provide anti-fibulin-3 antibodies, recombinant proteins that bind specifically to fibulin-3, compositions and the treatment methods comprising these antibodies and recombinant proteins.