Redirected infection of directly biotinylated recombinant adenovirus vectors through cell surface receptors and antigens

Abstract

The inability of adenovirus to infect primitive hematopoietic cells presents an obstacle to the use of adenovirus vectors for gene transfer to these cell types. Therefore, expanding the tropism of adenovirus vectors to unique cell surface antigens would be an important development for gene therapy protocols. In this study, we sought to redirect infection of adenovirus vectors to primitive human hematopoietic cells that universally express the c-Kit receptor on their cell surface. To accomplish this, a vector was constructed by covalently linking biotin molecules to recombinant adenovirus, followed by addition of the biotinylated ligand for the c-Kit receptor, stem cell factor (SCF), through an avidin bridge.

MicroPET imaging of Cre–loxP-mediated conditional activation of a herpes simplex virus type 1 thymidine kinase reporter gene

“…However, to apply the use of PRG in other Cre transgenic animals, such as those that express Cre recombinase in heart or prostate, the adenovirus injection via tail vein will likely not be very useful. In such transgenic animal models or in tumor models, either direct injection of the adenovirus at the specific site or redirected adenoviruses that use various molecular bridges such as peptide-targeting ligands, 39 bispecific antibodies 40 or directly biotinylated adenovirus vectors 41 are likely to be much useful. Alternatively, different gene delivery modalities such as liposomes 37 or PEI-PEG formulations 38 may also be useful.…”

Efficient infection of primitive hematopoietic stem cells by modified adenovirus

“…Moreover, the stimulation conditions themselves induce the cells to differentiate, 9,34 resulting in a loss of their pluripotency and often in increased toxicity. 8 Other approaches to infecting normal and malignant cells of the hematopoietic lineage have used lipofectamine, 35 bispecific antibodies that target both adenovirus epitopes and cell antigens, biotinylated adenoviruses 36 or adenoviruses with heparan sulfate binding domains. 37 These studies have generally required large amounts of vector and have not had proven success with highly primitive stem cell populations.…”

Recombinant single-chain antibodies with various oligopeptide tails for targeted gene delivery

“…1,2 Alternatively, certain biological activities such as ligands, receptors, antigens and antibodies have been challenged to select cell types. [3][4][5][6][7] These novel approaches have made substantial improvement, but yet further innovation has been in demand.…”