177 results about "Viral procapsid" patented technology

The disclosure relates to compositions and methods for the preparation, use, and / or formulation of adeno-associated virus capsid protein variants.

The disclosure relates to compositions and methods for the preparation, use, and / or formulation of adeno-associated virus capsid protein variants.

The invention provides a mutant of enterovirus 71 and virus-like particles thereof, and relates to the field of biological medicines. The enterovirus 71 type virus-like particle is obtained by modifying structural genes VP0, VP1 and VP3 of virus capsid protein by utilizing computational structure biology and completing self-assembly in vivo through a hansenula polymorpha expression system. Compared with the unmodified enterovirus 71 type mutant and the virus-like particles thereof, the enterovirus 71 type mutant and the virus-like particles thereof have the advantages that the immunogenicity can be obviously improved, and the clinical application prospect is relatively high.

The present invention relates to an exogenous target gene expression cassette for delivering an exogenous target gene to the retina, in particular AIPL1 to retinal pigment epithelial cells and photoreceptor cells, comprising an IRBP enhancer sequence, a rhodopsin kinase (RK) promoter sequence and a CAG intron sequence, which are operatively linked, and an exogenous target gene. The present invention also relates to a recombinant adeno-associated viral vector comprising a viral capsid comprising a capsid protein or a capsid protein variant and a viral vector genome comprising an expression cassette encoding for specifically expressing an exogenous target gene in retinal pigment epithelial cells and photoreceptor cells. The recombinant adeno-associated virus vector can be used for relieving or treating retinal degenerative eye diseases by intravitreal administration or subretinal administration.

Provided herein are recombinant adeno-associated virus (AAV) capsid proteins, compositions (e.g., rAAV) comprising the capsid proteins, nucleic acids encoding the capsid proteins, and methods of making and using the capsid proteins.

The present disclosure relates to novel adeno-associated adenovirus (AAV) vectors comprising targeting peptides. More particularly, the present disclosure relates to an adeno-associated serotype 2 virus vector, AAV2, comprising a transgene encoding LIGHT wherein the viral capsid of the AAV2 vector comprises a targeting peptide that alters its tropism to target tumor endothelial cells; and a use of the carrier. The disclosure also relates to the use of said vectors in therapy, in particular in the treatment of cancer.

Disclosed herein, in certain embodiments, are non-enveloped capsid delivery systems which comprise a viral capsid polypeptide and a heterologous cargo, as well as methods of making and using such non-enveloped capsid delivery systems.

Aspects of the present disclosure relate to compositions and methods useful for the treatment of nervous system diseases and disorders. In some embodiments, the disclosure provides methods of treating a nervous system disease or disorder comprising administering both a viral vector comprising an interfering nucleic acid (e.g., an artificial miRNA) and a viral vector comprising a CYP46A1 protein. In some embodiments, the disclosure provides methods of treating Huntington's disease comprising administering both a viral vector comprising an interfering nucleic acid (e.g., an artificial miRNA) targeting the Huntington's gene (HTT) and a viral vector comprising a CYP46A1 protein. In some embodiments, the viral vector comprises a modified viral capsid, for example, for preferentially targeting cells in the CNS or PNS.

The invention discloses a capsid inhibitor as well as a preparation method and application thereof. The capsid inhibitor can occupy a central hole of a virus capsid protein hexamer, so that nucleotide introduction is inhibited, reverse transcription in a virus capsid is effectively blocked, meanwhile, formation of capsid protein lattices is interfered, and the capsid inhibitor has excellent antiviral activity, for example, the capsid inhibitor shows remarkable anti-human immunodeficiency virus activity.

The technology described herein provides variant adeno-associated viral capsid polypeptides and viruses comprising the same. Further provided herein are methods for delivering a viral payload using viruses comprising variant capsid polypeptides described herein. Described herein are viral vectors comprising a variant sequence of the capsid gene, VP1. In particular, viral vectors with capsid polypeptide mutations that modify tropism of the viral particles relative to particles with wild-type capsid polypeptide are described.

Methods of determining the stoichiometry of a viral capsid and / or determining the heterogeneity of protein components in a viral capsid are described.

The invention relates to the field of biological medicine, and provides a coxsackie virus A16 type mutant and a virus-like particle thereof, compared with a wild type coxsackie virus A16 type, the mutant has at least one amino acid mutation site in the following regions: (1) a canyon region of a virus capsid; (2) a channel area at a secondary axis; or (3) a channel region at a quasi-tertiary axis. The mutant and the virus-like particle are obtained by optimizing and modifying structural proteins VP0, VP1 and VP3 which form a virus capsid by using computational biology and structural biology methods, co-expressing and co-assembling the structural proteins in a hansenula polymorpha expression system to form the virus-like particle, and then carrying out series of chromatographic purification. Compared with a non-mutated coxsackie virus A16 type virus-like particle mutation scheme, the coxsackie virus A16 type virus-like particle mutation scheme disclosed by the invention has the advantages that the antigen immunogenicity can be obviously improved, and the clinical application value is realized.

The application discloses an integrin-reformed specific heart and muscle targeting AAV9 dominant mutant. The application provides an adeno-associated virus capsid protein, which comprises a targeting peptide containing an amino acid sequence as shown in any one of SEQ ID NO: 1-28. According to the RGD sequence binding with integrin, the polypeptide specific binding principle, the random amino acid carrying and the construction of the diversified AAV capsid library, and the high-throughput screening of the AAV with the suitable capsid structure, the application successfully obtains a new adeno-associated virus vector with high heart and / or muscle transduction efficiency, and the new adeno-associated virus vector exhibits better heart and / or skeletal muscle targeting and transduction efficiency in an animal model, and the off-target expression in non-target tissues is significantly reduced, and the new adeno-associated virus vector has important scientific value and commercial prospect.

Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating the recombinant adeno-associated viral capsid proteins and a library from which the capsids are selected are also provided.

Provided herein are methods and systems for detecting polynucleotide sequences encoding viral capsids in metagenomic data. The methods and systems disclosed herein may include a sequence alignment-based module, a gene-based data processing module, and further characterization of putative viral sequences to identify novel polynucleotide sequences encoding viral capsids in metagenomic data.

The present application relates to (i) a variant adeno-associated virus (AAV) capsid polypeptide comprising a peptide insertion in the variable region IV or in the variable region VIII relative to a wild-type AAV capsid polypeptide, wherein the peptide insertion comprises an amino acid sequence selected from the group consisting of SEQ ID NOs:1-29 or an amino acid sequence having at least 70% sequence identity thereto, (ii) an isolated nucleic acid encoding the aforementioned variant polypeptide, (iii) a recombinant polynucleotide comprising the aforementioned nucleic acid, and (iv) an isolated cell comprising the aforementioned polypeptide, nucleic acid or recombinant polynucleotide. The present application further relates to (v) an adeno-associated virus (AAV) vector comprising the aforementioned variant polypeptide, (vi) a pharmaceutical composition comprising the aforementioned AAV vector as well as (vii) the use of the aforementioned vector or pharmaceutical composition in preventing or treating an ocular disease. Finally, the present application relates to (viii) a method of delivering a heterologous nucleic acid to a retinal cell and (ix) a method of delivering a heterologous nucleic acid to the eye of a subject.

The invention relates to a helper adenovirus genome wherein expression of one or more of the adenoviral early E1 genes, E2 genes including DNA-binding protein (DBP), pre-terminal protein (pTP) and DNA polymerase, or production of functional proteins are regulated. The invention also relates to a process for delivery of the helper-dependent or gutless adenovirus vector genome and modulating replication of the helper virus DNA in the manufacturing cells, in which to allow a sufficient length of time before excision, cutting, or recombination to removal of the viral packaging signal DNA sequence from the helper adenovirus genome prior to induction of viral DNA replication, and expression of helper proteins that are required for adenovirus capsid particle formation and packaging, or encapsidation, of the helper-dependent or gutless adenovirus vector genomes, while preventing the packaging, or encapsidation, of the helper adenoviral genome into preform adenoviral capsids.

The present disclosure relates to chimeric adeno-associated virus capsids and related adeno-associated viruses targeting glial progenitor cells.

Provided herein are recombinant adeno-associated virus (AAV) capsid proteins, compositions (e.g., rAAV) comprising the capsid proteins, nucleic acids encoding the capsid proteins, and methods of making and using the capsid proteins.

The present disclosure relates to compositions of surface modified viral capsids having high physical titers. The present disclosure also relates to a method of preparing surface modified viral capsids using an efficient process of (a) reacting (i) a viral capsid comprising a plurality of surface available primary amines and (ii) a capsid-reactive linker comprising a terminal tetrafluorophenyl (TFP) ester and a first member of a crosslinker reactive pair to provide a composition comprising surface functionalized viral capsid; and (b) reacting the composition comprising surface functionalized viral capsid with a functionalized ligand comprising a second member of the crosslinker reactive pair.

The present disclosure relates to compositions of surface modified viral capsids having high physical titers. The present disclosure also relates to a method of making a surface modified viral capsid using an efficient process of (a) reacting (i) a viral capsid comprising a plurality of surface accessible primary amines and (ii) a capsid-reactive linker comprising a terminal tetrafluorophenyl (TFP) ester and a first member of a cross-linking agent reactive pair, to provide a composition comprising a surface functionalized viral capsid; and (b) reacting the composition comprising the surface functionalized viral capsid with a functionalized ligand comprising a second member of the crosslinker reactive pair.

The present invention relates to the technical field of prevention and control of aquatic animal diseases, and specifically relates to a nanocomposite for a nervous necrosis virus, a preparation method therefor, and the use thereof. Provided in the present invention is a nanocomposite consisting of poly(lactic-co-glycolic acid), polyethyleneimine and a siRNA. Also provided in the present invention are a preparation method for the nanocomposite and the use thereof in the preparation of a drug for improving the survival rate of fish eggs infected with a nervous necrosis virus. The present invention constructs a vector for a capsid protein of the nervous necrosis virus by means of simulating the nervous necrosis virus and expresses same in cells, and screens out a siRNA that can effectively inhibit the expression of the viral capsid protein, thus constructing the nanocomposite for the nervous necrosis virus. The nanocomposite can block NNVs at the embryonic phase (fertilized eggs), thereby improving the survival rate of fish fry, and further opening up new possibilities for the treatment of early stage diseases in fish fry. The method is innovative in the field of artificial breeding of aquatic animals and provides new ideas for virus prevention and control in the field of aquaculture.

This application provides a novel differentiation factor for direct cross-differentiation from somatic cells to motor neurons, a composition containing the differentiation factor, a method for direct cross-differentiation using the composition, and uses for the novel differentiation factor. [Solution] A composition for direct cross-differentiation from somatic cells to induced motor neurons, the composition comprising (A) the Gsta4 protein or nucleic acid coding therefor; and (B) one or more proteins selected from Ascl1, Brn2, Myt1L, Hb9, ISL1, Lhx3, Ngn2 and NeuroD1 or nucleic acid coding therefor; and further comprising a viral capsid for transmitting (A) or (B).

Provided are an adeno-associated virus mutant and the use thereof. The amino acid sequence of the adeno-associated virus capsid protein mutant comprises a sequence shown as any one of SEQ ID Nos. 1-6. Further provided is the use of the adeno-associated virus capsid protein mutant and an expression vector, host cell and recombinant adeno-associated virus thereof in the preparation of a drug delivery tool for preventing and / or treating muscle or cardiac diseases. The provided adeno-associated virus capsid protein mutant has muscle or heart targeting ability, the muscle targeting ability is increased by a maximum of about 496.41 times, the liver and spleen tropism is nearly 100 times lower than that of a control group, and said mutant has good specificity, and exhibits good effect in NHPs.

The invention relates to a helper adenovirus genome wherein expression of one or more of the adenoviral early E1 genes, E2 genes including DNA-binding protein (DBP), pre-terminal protein (pTP) and DNA polymerase, or production of functional proteins are regulated. The invention also relates to a process for delivery of the helper-dependent or gutless adenovirus vector genome and modulating replication of the helper virus DNA in the manufacturing cells, in which to allow a sufficient length of time before excision, cutting, or recombination to removal of the viral packaging signal DNA sequence from the helper adenovirus genome prior to induction of viral DNA replication, and expression of helper proteins that are required for adenovirus capsid particle formation and packaging, or encapsidation, of the helper-dependent or gutless adenovirus vector genomes, while preventing the packaging, or encapsidation, of the helper adenoviral genome into preform adenoviral capsids.

The present disclosure provides AAV capsid proteins comprising a modification in the amino acid sequence and virus vectors comprising the modified AAV capsid protein. The disclosure also provides methods of administering the virus vectors and virus capsids of the disclosure to a cell or to a subject in vivo. This disclosure also relates to recombinant adeno associated virus (rAAV) capsid proteins comprising one or more amino acid substitutions in the 5-fold region of the rAAV capsid that result in decreased reactivity to neutralizing antibodies, and their use as gene delivery vehicles.

The present invention relates to the fields of medicine, molecular biology, and gene therapy. In particular, the invention relates to novel recombinant adeno-associated virus capsids, uses thereof and methods of manufacturing.

Provided herein are compositions and methods of utilizing engineered viral capsid for therapeutic delivery. Also provided herein are methods of using the provided compositions and methods for delivering therapeutic for treating diseases.

Provided are gene therapy vectors designated MEV-GTVs, which are MEVs that contain an ITR-containing plasmid (also referred to as a minigene plasmid) that comprises Inverted Terminal Repeats (ITRs), such as viral ITRs, and nucleic acid encoding a product of interest, and optionally regulatory sequences. The ITRs serve to circularize the minigene plasmid. The plasmids do not contain additional viral components, so that resulting DNA is not encapsulated in a viral capsid or envelop and is not replicated by viral genes. The plasmids can be inserted into bacterial plasmids for propagation.

The invention relates to the field of biological medicine, and discloses a fusion type novel adeno-associated virus and application thereof. The invention provides a fusion type adeno-associated virus AAV2-ACM202 capsid protein. The fusion type adeno-associated virus AAV2-ACM202 capsid protein is obtained by inserting a polypeptide as shown in SEQ ID No: 4 into a 587 site and a 588 site of an amino acid sequence of a wild type adeno-associated virus AAV2 capsid protein. The fusion adeno-associated virus provided by the invention is administrated through intravitreal injection, can efficiently and specifically infect retinal ganglion cells in eyes, and can be widely applied to gene therapy of related diseases.