The present disclosure describes the generation and the use of Ad variants (Ad) possessing any combination of mutations in genes that code for the hexon, penton, fiber, and non-structural proteins, where simultaneous modification of hexon and penton are made to avoid the trapping of Ad in the liver and to reduce toxicity after intravascular virus administration. Such liver de-targeted Ad can be useful tool for selective and specific gene delivery to extra-hepatic tissues and cells, including disseminated metastatic cancer cells.

The invention discloses a human adenovirus species C having a capsid which comprises a modified adenovirus hexon protein, wherein the modified adenovirus hexon protein has a modified HVR1 region, wherein the modified HVR1 region has the sequence DEAATALEINLKKKKQAEQQ (SEQ ID NO.: 1). The invention further discloses the adenovirus of the disclosure for use in treating or preventing a human disease. The invention further discloses a nucleic acid encoding the modified adenovirus hexon protein. The invention further discloses the use of an adenovirus according to the disclosure for transducing mesenchymal stromal cells (MSCs) or tumor cells. The invention further discloses an in vitro method for transducing MSCs and a transduced MSC obtainable by the method. The invention further discloses the transduced MSC of the disclosure for use in treating a disease.

This invention relates to preparations comprising adenoviral vectors with modified capsid proteins. These modified capsid proteins enable customisable decoration of the adenoviral vector to be performed, enabling diverse applications from personalised cancer vaccines to targeted gene therapy vectors, and mixtures of the same. In particular, the adenoviral vectors with modified capsid proteins may be modified in the hexon and/or pIX capsid proteins. The invention makes use of peptide pairs to provide a “primed” adenovirus which is ready for decoration.

This invention provides methods and materials for treating cancer. The invention encompasses methods and materials for delivering programmed death-ligand 1 (PD-L1) binding compounds and/or compositions containing one or more monovalent or multivalent programmed death-ligand 1 (PD-L1) binding compounds which are administered to a mammal having cancer to treat the mammal. In some cases, a multivalent PD-L1 binding compound can include two or more programmed cell death protein 1 (PD-1) polypeptides (and/or fragments thereof having the ability to bind PD-L1). This invention also provides methods and materials for making multivalent PD-L1 binding compounds and methods and materials for making nucleic acid molecules that encode PD-L1 binding compounds.

Disclosed herein are methods and compositions for inactivating CCR-5 genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs, such as adenovirus (Ad) vectors, and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also provided.

The invention relates to a recombinant adenovirus nucleic acid wherein the gene encoding protein V and/or the gene encoding protein VII is placed under control of a heterologous promoter, to a recombinant adenovirus nucleic acid wherein the adenoviral nucleotide sequence is mutated in such a way that it is no longer capable of producing one or more of the coat proteins, to cellular vesicles filled with such adenoviral material, cells provided with such adenoviral material and to methods and use thereof.

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 present disclosure describes the generation and the use of Ad variants (Ad) possessing any combination of mutations in genes that code for the hexon, penton, fiber, and non-structural proteins, where simultaneous modification of hexon and penton are made to avoid the trapping of Ad in the liver and to reduce toxicity after intravascular virus administration. Such liver de-targeted Ad can be useful tool for selective and specific gene delivery to extra-hepatic tissues and cells, including disseminated metastatic cancer cells.

The present invention relates to cancer therapies. More specifically, the present invention relates to oncolytic adenoviral vectors and cells and pharmaceutical compositions comprising said vectors. The present invention also relates to a use of said vectors in the manufacture of a medicament for treating cancer in a subject and a method of treating cancer in a subject. Furthermore, the present invention relates to methods of producing peptidylarginine deiminase and TIMP in a cell and increasing anti-tumor effect and induction of specific immune response in a subject, as well as uses of the oncolytic adenoviral vector of the invention for producing transgenes in a cell and increasing anti-tumor effect and generation of specific immune response in a subject.

Synthetic adenoviruses having chimeric fiber proteins and liver detargeting mutations are described. The synthetic adenovirus vectors are capable of specifically infecting cells at wound sites or in regions of damaged tissue. The synthetic adenovirus vectors also are capable of expressing transgenes, such as wound healing factors, at sites of wounded or damaged tissue. Accordingly, the described vectors can be used to detect wounded or damaged tissue, and/or to promote wound healing and regeneration of damaged tissue, such as by expression of heterologous wound healing or tissue regeneration factors.