Figure 1. A generalized adenovirus structure depicting major structural components of a wild-type adenovirus capsid. Hexon is depicted as a hexagon with 12 homotrimers per capsid face (only 12 of 240 trimers are shown). The penton-base, comprised of five subunits at each vertex, and trimeric fibre and pIX structures are shown. Adenovirus serotype 2 and 5 capsids contain a 36-kilobase double-stranded DNA genome (not shown).

Figure 2. A schematic representation of genetically altered fibres for adenovirus targeting. (See text for specific examples of each genetic targeting approach and targeting moiety used.) (a) Trimeric wild-type adenovirus fibre; tail, shaft and knob regions are shown. (b) Pseudotyped chimaeric fibre bearing an alternate human or animal serotype knob domain. (c) Fibre knob containing a C-terminal targeting ligand. (d) Fibre knob with a constrained targeting peptide in the flexible H–I loop. (e) ‘de-knobbed’ fibre containing a heterologous trimerization sequence and a C-terminal targeting moiety.

Figure 3. The two-step adenovirus infection pathway. Shown are the basic steps of initial high-affinity binding of the virion fibre to its primary cellular receptor, CAR, followed by endocytic cell entry mediated by penton-base RGD interaction with cell-surface integrins. Upon endosomal lysis, the partially dismantled virion is then released into the cytoplasm and is actively translocated to the nuclear pore complex where complete capsid degradation and viral genome import is accomplished.

Figure 4. Adapter molecules for receptor-specific adenovirus targeting. A generalized adapter molecule ablates native CAR-based tropism and targets adenovirus to an alternate cellular receptor molecule. The dual specificity of the adapter molecule for both the adenovirus and the alternative receptor provides novel, CAR-independent cell binding.