The present inventions provide covalently surface modified adeno-associated viruses can comprise gene of interest (GOIs) and advantageously can be targeted to certain cell and tissue types for preventative and therapeutic purposes. The present inventions further provide systems and methods for engineering adeno-associated virus (AAV) to create covalently surface modified adeno-associated viruses, and methods of purifying such covalently surface modified adeno-associated viruses. The inventions further include covalently surface modified adeno-associated viruses and preparations and products comprising such covalently surface modified adeno-associated viruses.

Provided herein are compositions and methods for the viral gene therapy (e.g., AAV-directed gene therapy) of cholesterol storage diseases or disorders, such as Niemann-Pick disease, Type C.

A method for treating a bone and soft tissue tumor, including administering a conditionally replicating adenovirus having a E1A gene under expression control of a Survivin promoter, to a subject in need thereof. A conditionally replicating adenovirus including a E1A gene under expression control of a Survivin promoter and the conditionally replicating adenovirus is not defective in a E3 region.

An african swine fever virus vaccine includes five groups of antigens in total, and each group is respectively obtained by constructing recombinant adenovirus vectors co-expressing four antigen genes of african swine fever virus, and packaged by 293TD37 cells. The four antigenic genes of African swine fever virus in each group are 1, P72, B602L, P30 and P54; 2, CP129Rubiqutin, MGF5L6L, CP312R, and MGF110-4L; 3, L8Lubiqutin, I215L, I73RHBsAgHBsAg and E146L; 4, EP402R, EP153R, I177L, and K205Rubiqutin; 5, F317L, A151R, P34, and pp62. The construction of the recombinant adenovirus vector for co-expression of four antigen genes of the african swine fever virus mainly includes: knocking out E1, E3, E2a and E4 genes of the adenovirus vector by CRISPR/cas9 technology, constructing an ORF6/7 expression frame of E4 in an E2a region, and constructing shuttle plasmids in E1 and E4 regions for appropriately expressing four antigen genes, thereby obtaining a completely new adenovirus vector.

The present application provides compositions and methods for increasing safety, selectivity, and efficacy of transduction of human cells, including human long-term repopulating and hematopoietic stem cells (LT-HSC) and human cancer cells, by adenovirus vectors through multiplexed targeting of virus attachment and internalization receptors. Multiplexing targeting Ad vector receptor specificities through the combination of i) restricting fiber-specific attachment receptors, ii) deleting the RGD amino acid motif from the penton base protein, and iii) inserting into Ad penton base protein of peptides that lack the RGD amino acid motif and enable vector interaction with integrin classes expressed on target cells, allows for the improvement of safety, selectivity, and efficacy of vector-mediated transduction of human cells in vitro and after intravenous vector administration in vivo.

An adenovirus that reduces the extent to which neutralizing antibodies bind to the adenovirus has an AB loop that includes a sufficient portion of the amino acid sequence VTINRSA (amino acids 8-14 of SEQ ID NO:2), TYMLSRN (amino acids 8-14 of SEQ ID NO:3), or STMGTSH motif (amino acids 8-14 of SEQ ID NO:4) to reduce binding of neutralizing anti-adenovirus antibodies compared to an adenovirus having a wild-type AB loop. In some cases, another aspect, the adenovirus has an AB loop that includes a sufficient portion of the amino acid sequence VTINRSA (amino acids 8-14 of SEQ ID NO:2), TYMLSRN (amino acids 8-14 of SEQ ID NO:3), or STMGTSH motif (amino acids 8-14 of SEQ ID NO:4) to reduce hemagglutination compared to an adenovirus having a wild-type AB loop. The adenovirus can be used to deliver therapy to a target cell to which the AB loop binds.

The present disclosure provides methods for preparing digested virus proteins, including adenovirus and adeno-associated virus capsid proteins, from a sample of virus proteins, as well as methods of analyzing such digested virus proteins via liquid chromatography-tandem mass spectrometry. The methods include the use of a mixture of sodium deoxycholate (SDC) and N-dodecyl-beta-D-Maltoside (DDM) to rapidly and easily prepare the digested virus proteins.

A mutant E1A antagonizing ubiquitination-mediated degradation and its use in the preparation of potentiated oncolytic adenoviruses and immune potentiators are provided. The mutant E1A is obtained by mutating lysine residues at positions 253 and 285 of a wild-type E1A to any one of glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, tyrosine, tryptophan, serine, threonine, cysteine, methionine, asparagine, glutamine, aspartic acid, glutamic acid, arginine, or histidine. The mutation is capable of reducing the degradation of a key adenoviral replication protein E1A and maintaining its high level expression, thereby promoting replication of oncolytic adenovirus, improving tumor killing effect, and holding broad clinical application prospects.

Compositions comprising a modified adenovirus AD5.F35 which includes coding sequence of soluble GUCY2C extracellular domain sequences are disclosed. Compositions comprising a Listeria monocytogenes vector which includes coding sequence of soluble GUCY2C extracellular domain sequences are disclosed. Methods of treating individuals diagnosed with cancer/tumors expressing GUCY2C methods of preventing micro-metastasis are disclosed.

The present disclosure includes adenoviral vectors characterized by efficient transduction of hematopoietic cells (e.g., one or more particular types of hematopoietic cells), e.g., for in vivo or ex vivo gene therapy. The present disclosure includes, among other things, Ad3, Ad5, Ad7, Ad11, Ad14, Ad16, Ad21, Ad34, Ad35, Ad37, and Ad50 vectors and genomes. Ad3, Ad5, Ad7, Ad11, Ad14, Ad16, Ad21, Ad34, Ad35, Ad37, and Ad50 vectors and genomes of the present disclosure can include therapeutic payloads.