Abstract: 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.

Abstract: 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.

Abstract: The present invention describes generation and the use of adenovirus variants (Ad) possessing modified capsid penton base protein where mutations in the penton based RGD loop are made to avoid Ad binding to cellular ?3-integrins. Specifically, the ablation of Ad penton base interaction with cellular ?3-integrins results in reduced activation of inflammation after intravenous Ad administration. Further, the introduction into penton RGD loop of non-RGD containing peptides, which mediate virus entry into the cell via new cellular receptors, allows for the efficient Ad-mediated gene delivery into target cells in vivo after intravascular virus administration and triggers significantly reduced toxicity associated with Ad injection.