Selective targeting of human cells by a chimeric adenovirus vector containing a modified fiber protein

Stevenson, Susan C.; Rollence, Michele L.; Marshall-Neff, Jennifer; McClelland, Alan

doi:10.1128/jvi.71.6.4782-4790.1997

Cited by 159 publications

(37 citation statements)

References 24 publications

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“…This confirmed that an 'Ad5' vector possessing Ad3 tropism had been produced. A similar strategy was reported by Stevenson and colleagues 38 who also demonstrated differences in the gene transfer efficiency of various cell lines depending on whether wild-type or chimeric fiber vectors were used. 38 After the initial proof of principle, incorporation of specific targeting ligands was investigated.…”

Section: Genetic Retargetingmentioning

confidence: 70%

Strategies to Adapt Adenoviral Vectors for Targeted Delivery

Curiel¹

1999

Annals of the New York Academy of Sciences

136

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The utility of current generation adenoviral vectors for targeted, cell-specific gene delivery is limited by the promiscuous tropism of the parent virus. To address this issue, we have developed both genetic and immunologic methods to alter viral tropism. Immunologic retargeting has been achieved via conjugates comprised of an antifiber knob Fab and a targeting moiety consisting of a ligand or antireceptor antibody. Gene delivery by this approach has been accomplished via a variety of cellular pathways including receptors for folate, FGF, and EGF. In addition to cell-specific gene delivery, this strategy has allowed enhanced gene delivery to target cells lacking the native adenoviral receptor, CAR. Of note, this specific and extended gene delivery allowed enhanced survival in murine models of human carcinoma via cancer gene therapy. Genetic strategies to alter adenoviral tropism have included both fiber modification and fiber replacement. In the former, we have identified the HI loop of fiber as a propitious locale for introduction of heterologous peptides. Incorporation of an RGDC peptide at this locale allowed gene delivery via cellular integrins with dramatic efficiency augmentations. As a strategy to achieve both new tropism as well as to ablate native tropism, methods have been developed to replace the fiber protein with heterologous motif which preserves the key trimeric quaternary structure of fiber and allows for propagation. Such a fiber-replacement virus has been rescued and has demonstrated capacities consistent with its utility as a novel vector agent. These strategies have allowed the achievement of cell-specific gene delivery via adenoviral vectors and thus have the potential to enhance the utility of this vector agent.

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Section: Genetic Retargetingmentioning

confidence: 70%

Strategies to Adapt Adenoviral Vectors for Targeted Delivery

Curiel¹

1999

Annals of the New York Academy of Sciences

136

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“…Similarly, replica-tion-competent or replication-defective viral vectors derived from Ad7 have been used for vaccine strategies (Abrahamsen et al, 1997;Lubeck et al, 1989;Nan et al, 2003). An extended tropism was also demonstrated for fiber swapped Ad vectors containing fibers of species B viruses such as Ad3 (Kanerva et al, 2002;Stevenson et al, 1997;Von Seggern et al, 2000), Ad11 (Stecher et al, 2001), and Ad35 Havenga et al, 2002;Knaan-Shanzer et al, 2001;Rea et al, 2001;Shayakhmetov et al, 2000;Yotnda et al, 2001). To generate a tool for characterization of host cell -Ad3 interactions, we constructed a recombinant E1-deleted Ad3 vector expressing eGFP using the bacterial artificial chromosome (BAC) strategy, and we report here the complete nucleotide sequence of serotype Ad3 (GB) (GenBank accession no.…”

Section: Introductionmentioning

confidence: 98%

The nucleotide sequence and a first generation gene transfer vector of species B human adenovirus serotype 3

Sirena

Ruzsics²,

Schaffner

et al. 2005

Virology

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Human adenovirus (Ad) serotype 3 causes respiratory infections. It is considered highly virulent, accounting for about 13% of all Ad isolates. We report here the complete Ad3 DNA sequence of 35,343 base pairs (GenBank accession DQ086466). Ad3 shares 96.43% nucleotide identity with Ad7, another virulent subspecies B1 serotype, and 82.56 and 62.75% identity with the less virulent species B2 Ad11 and species C Ad5, respectively. The genomic organization of Ad3 is similar to the other human Ads comprising five early transcription units, E1A, E1B, E2, E3, and E4, two delayed early units IX and IVa2, and the major late unit, in total 39 putative and 7 hypothetical open reading frames. A recombinant E1-deleted Ad3 was generated on a bacterial artificial chromosome. This prototypic virus efficiently transduced CD46-positive rodent and human cells. Our results will help in clarifying the biology and pathology of adenoviruses and enhance therapeutic applications of viral vectors in clinical settings.

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“…The adenovirus fiber protein is a major determinant of adenovirus tropism (Gall et al, 1996;Stevenson et al, 1997). The fiber protein extends from the capsid and mediates viral binding to the cell surface by binding to cell surface receptors (Philipson et al, 1968).…”

Section: Introductionmentioning

confidence: 99%

A 50-kDa Membrane Protein Mediates Sialic Acid-Independent Binding and Infection of Conjunctival Cells by Adenovirus Type 37

Fernandez

Fleck

et al. 2001

Virology

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The ocular tropism of adenovirus type 37 (Ad37) does not correlate with the wide distribution of the 46-kDa coxsackievirus and adenovirus receptor (CAR), the major receptor for most adenovirus serotypes. We previously found that Ad37 infects and binds well to conjunctival cells (Chang C), but poorly to lung epithelial (A549) cells that express CAR and hypothesized that this serotype uses a distinct receptor that is selectively expressed on conjunctival cells. To test this, we produced particles of a fiber-deleted Ad5 vector containing the Ad37 fiber protein. The "pseudotyped" vector infected Chang C cells better than A549 cells using a CAR-independent pathway. Ad37 binding was calcium-dependent and was abolished by protease digestion of cell surface proteins. Using a virus overlay protein blot assay (VOPBA), we detected calcium-dependent Ad37 binding to 50- and 60-kDa membrane proteins on permissive Chang C cells. In contrast, calcium-dependent binding was detected with only the 60-kDa protein on nonpermissive A549 cells. Ad19p, a closely related serotype that failed to bind to conjunctival cells, recognized the 60-kDa, but not the 50-kDa, protein. Ad37 has been reported to use sialic acid instead of CAR as a cell receptor on A549 cells. Pretreatment of Chang C cells with neuraminidase abolished Ad37 binding to only the 60-kDa protein, suggesting that sialic acid mediates Ad37 binding to the 60-kDa protein. The pseudotyped Ad37 vector was also able to infect neuraminidase-treated Chang C cells. Thus, subgroup D adenoviral binding to the 50-kDa protein is calcium-dependent and cell type- and serotype-specific, whereas binding to the 60-kDa protein is not necessary for infection of conjunctival cells. Together, these data suggest that the 50-kDa protein is the major receptor for Ad37 on conjunctival cells.

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Selective targeting of human cells by a chimeric adenovirus vector containing a modified fiber protein

Cited by 159 publications

References 24 publications

Strategies to Adapt Adenoviral Vectors for Targeted Delivery

Strategies to Adapt Adenoviral Vectors for Targeted Delivery

The nucleotide sequence and a first generation gene transfer vector of species B human adenovirus serotype 3

A 50-kDa Membrane Protein Mediates Sialic Acid-Independent Binding and Infection of Conjunctival Cells by Adenovirus Type 37

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