Transductional and transcriptional targeting of adenovirus for clinical applications.
Adenovirus (Ad) targeting is a novel approach for the design and administration of therapeutic agents wherein the agent is rationally designed to localize and restrict transgene expression to the site of disease in a self-directed manner, usually via exploitation of unique biophysical and genetic properties specific to the diseased tissue. The ablation of promiscuous native Ad tropism coupled with active targeting modalities has demonstrated that innate gene delivery efficiency may be retained while circumventing Ad dependence on its primary cellular receptor, the coxsackie and adenovirus receptor (CAR), to achieve CAR-independent vector tropism. Herein, we describe advances in Ad targeting that are predicated not only on fundamental understanding of vector/cell interplay, but also on the specific transcriptional profiles of target tissues. Further, targeting is discussed in the context of improving the safety and efficacy of clinical approaches utilizing adenoviral vectors and replication competent oncolytic agents. In summary, existing results suggest a critical linkage between targeted agents and increases in therapeutic utility.
Glasgow
J N
JN
Division of Human Gene Therapy, Department of Medicine, University of Alabama at Birmingham, USA.
Bauerschmitz
G J
GJ
Curiel
D T
DT
Hemminki
A
A
D000256:Adenoviridae / Q000235:genetics*; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D004268:DNA-Binding Proteins / Q000235:genetics; D051766:Early Growth Response Protein 1; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics; D009369:Neoplasms / Q000628:therapy; D011401:Promoter Regions, Genetic; D011991:Receptors, Virus / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D014161:Transduction, Genetic
C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D011991:Receptors, Virus; D014157:Transcription Factors