While direct proof is lacking, GRF1/3 may function not only as transcriptional activators or transcriptional repressors but also oppositely regulate genes that share common function or even genes that belong to the same gene family. This bifunctional activity, which reveals an unexpected degree of complexity of GRF1/3 in the regulation of their targets, may count among the main characteristics of key genes linking plant growth and developmental pathways to defense signaling. Recombinant adenoviruses are in pre-clinical and clinical development as oncolytic agents and vectors for vaccination and gene therapy. Such Ad-based drugs can considerably benefit from or even depend on a cell type-specific mode of action in order to limit side effects, while retaining therapeutic potency. Cell type-specificity of Ad-based vectors and oncolytics has been well established at the post-entry level by transcriptional targeting and microRNA regulation. In MRS 2578 contrast, targeting of Ad cell entry, which would better avoid side effects and virus sequestration, remains a challenge. Genetic strategies for Ad entry targeting facilitate simple clinical grade production and ensure that Catharanthine sulfate progeny oncolytic Ads produced in the patients�� tumors retain the improved properties. However, strategies for genetic entry targeting of Ads are hampered by the rigid Ad capsid structure, inability of antibody molecules, as preferred targeting moieties, to fold properly after fusion to cytosolically expressed Ad capsid proteins, and the complex interactions of host factors modulating Ad cell entry in patients. Entry targeting of Ads requires two steps: ablation of native tropism for healthy cells and re-targeting of a receptor specifically expressed on target cells by insertion of a corresponding ligand into the Ad capsid. Cell entry of native Ads is initiated by binding of the capsid protein fiber to the attachment receptor, which is Coxsackie-Ad receptor for the most widely used serotype HAdV-5. Virus internalization is then triggered by binding of the penton base to cellular integrins. For therapeutic applications of Ads not intended to target hepatic tissue, liver de-targeting is of key importance to avoid toxic side effects.