Adenovirus receptors and their implications in gene delivery

Abstract

Adenoviruses (Ads) have gained popularity as gene delivery vectors for therapeutic and prophylactic applications. Ad entry into host cells involves specific interactions between cell surface receptors and viral capsid proteins. Several cell surface molecules have been identified as receptors for Ad attachment and entry. Tissue tropism of Ad vectors is greatly influenced by their receptor usage. A variety of strategies have been investigated to modify Ad vector tropism by manipulating the receptor-interacting moieties. Many such strategies are aimed at targeting and/or detargeting of Ad vectors. In this review, we discuss the various cell surface molecules that are implicated as receptors for virus attachment and internalization. Special emphasis is given to Ad types that are utilized as gene delivery vectors. Various strategies to modify Ad tropism using the knowledge of Ad receptors are also discussed.

Advances in Gene Delivery Systems

“…[6] There are over 100 adenoviral serotypes identified that can infect and replicate in a wide range of organs, including 51 classified into six subgroups (A-F). [38,39] Of these, serotypes 2 and 5 in subgroup B are the most characterized viruses.…”

“…Viral fibre proteins bind to the Coxsackievirus and adenovirus receptor of the target cells to initiate the infection. [39,44] Internalization occurs via receptor-mediated endocytosis followed by release from the endosome. [45] Once inside the cytoplasm, the viral capsid undergoes disassembly as it migrates to the nuclear pore.…”

Gene Therapy of Glioblastoma Multiforme - Clinical Experience on the Use of Adenoviral Vectors

“…To date, more than 100 adenovirus serotypes have been classified, of which 51 serotypes are human adenoviruses, divided into seven species (human adenovirus A to F). These classifications are based on their hemagglutination properties, oncogenic potential in newborn hamsters, genomic organization and DNA homology (Sharma et al, 2009). Adenoviruses are non-enveloped, icosahedral viruses of 80 to 1200 nm in diameter.…”

“…The double stranded DNA genome is located in the virion core with DNA associated proteins and terminal proteins that serve as a primer for DNA replication. Human adenoviruses are known to cause a variety of clinical symptoms, depending on their serotypes (Sharma et al, 2009). These include infections of the upper and lower respiratory tract, renal and urinary tract, gastroenteritis and ocular infections.…”

“…In addition, approaches such as gene delivery of antisense or small interference RNAs (siRNA) targeted to growth factors in order to increase the sensitivity of glioma cells to chemotherapeutics or to inhibit migration and invasion of glioma cells have been developed. The most extensively studied and used adenoviral serotype in gene therapy is the serotype 5, causing only mild or asymptomatic infections (Sharma et al, 2009, Raty et al, 2008. In the first generation of adenoviral vectors, the E1 region encoding for early viral proteins is replaced by the transgene, making the vectors replication defective.…”