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Cheng, Xuan; Xin, Ming; Croyle, Maria A.

doi:10.1023/a:1025714412337

Cited by 40 publications

(12 citation statements)

References 30 publications

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“…In contrast, the SC-Ad vectors, can amplify antigen production during vaccination, but avoid the risk of adenovirus infection. They may particularly useful by the oral route, since most Ads are nearly quantitatively destroyed by stomach pH and digestive enzymes (Cheng et al, 2003). Therefore, RC-Ad4 and Ad7 vaccines were likely efficacious because they were able to amplify antigen production from the reduced number of cells that were infected by this stringent route.…”

Section: Discussionmentioning

confidence: 99%

IIIa deleted adenovirus as a single-cycle genome replicating vector

Crosby

Barry

2014

Virology

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Replication competent adenovirus (RC-Ad) vectors mediate robust transgene expression by virtue of amplifying transgenes by replication, but also put patients at a risk of frank adenovirus infection. In contrast, E1-deleted replication defective Ad (RD-Ad) vectors are safer, but produce substantially less transgene product. To generate a robust, but safer adenoviral vector, we created a “single cycle" adenovirus (SC-Ad) vector that replicates its genome and transgene, but that does not cause adenovirus infections by deleting the capsid cement protein IIIa in low seroprevalence adenovirus serotype 6. Ad6-ΔIIIa can be produced in IIIa-expressing cell lines. In normal cells, Ad6-ΔIIIa replicates its genome and transgene, but fails to package its DNA or form mature virus. SC-Ad and RC-Ad expressed transgenes hundreds of times higher than RD-Ad in human and mouse cells in vitro and in vivo in mice. These data suggest that SC-Ads may be safer amplifying vectors for vaccine and therapeutic applications.

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Section: Discussionmentioning

confidence: 99%

IIIa deleted adenovirus as a single-cycle genome replicating vector

Crosby

Barry

2014

Virology

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“…They went on to demonstrate that oral administration of the “stealth” PEGylated formulations to rats led to increased absorption of a poorly water soluble drug, danazol [160]. Cheng and coworkers PEGylated adenoviral vectors to improve their stability for oral administration as gene delivery vectors for colorectal cancer [161]. They covalently attached one of three different types of functionalized 5 kDa PEG to the free lysine groups on the protein capsids, and found that PEGylation with all three types of PEG actually increased the efficiency of transduction efficiency in differentiated enterocytes.…”

Section: Non-systemic Applications For Improved Delivery With Pegymentioning

confidence: 99%

“…They selected the vectors PEGylated with succinimidyl succinate functionalized PEG (SSPEG) for in vivo oral administration studies, finding significantly increased reporter protein expression throughout the GI tract (40-times higher expression in the colon) with the SSPEG vector compared to the unmodified adenoviral vector. Additional characterization of the internalization of SSPEG vectors by Caco-2 cells suggested that although they PEGylated 70-80% of the available attachment sites on the viral capsid, the PEGylation appeared to actually change the type of receptor interaction that led to internalization, which may have also led to increased gene transduction in vivo [161]. …”

Section: Non-systemic Applications For Improved Delivery With Pegymentioning

confidence: 99%

PEGylation as a strategy for improving nanoparticle-based drug and gene delivery

Suk

Kim

et al. 2016

Advanced Drug Delivery Reviews

3,042

2,076

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Coating the surface of nanoparticles with polyethylene glycol (PEG), or “PEGylation”, is a commonly used approach for improving the efficiency of drug and gene delivery to target cells and tissues. Building from the success of PEGylating proteins to improve systemic circulation time and decrease immunogenicity, the impact of PEG coatings on the fate of systemically administered nanoparticle formulations has, and continues to be, widely studied. PEG coatings on nanoparticles shield the surface from aggregation, opsonization, and phagocytosis, prolonging systemic circulation time. Here, we briefly describe the history of the development of PEGylated nanoparticle formulations for systemic administration, including how factors such as PEG molecular weight, PEG surface density, nanoparticle core properties, and repeated administration impact circulation time. A less frequently discussed topic, we then describe how PEG coatings on nanoparticles have also been utilized for overcoming various biological barriers to efficient drug and gene delivery associated with other modes of administration, ranging from gastrointestinal to ocular. Finally, we describe both methods for PEGylating nanoparticles and methods for characterizing PEG surface density, a key factor in the effectiveness of the PEG surface coating for improving drug and gene delivery.

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“…For example, crosslinking synthetic polymers onto the vector can reduce neutralization by anti-virus antibodies as well as enable evasion of innate immune responses, thereby enhancing gene transfer in the presence of existing antibodies and facilitating repeated administration by reducing subsequent adaptive immune responses to the vector (Kreppel and Kochanek, 2008). Polymeric materials that have been explored in conjunction with adenoviral and adeno-associated viral vectors have included polyethylene glycol (PEG; O’Riordan et al, 1999; Croyle et al, 2000, 2005; Cheng et al, 2003; De Geest et al, 2005; Eto et al, 2005; Lee et al, 2005; Mok et al, 2005; Oh et al, 2006; Hofherr et al, 2007), poly- N -(2-hydroxypropyl) methacrylamide (poly-HPMA; Fisher et al, 2001; Green et al, 2008), polysaccharides (Espenlaub et al, 2008), and others (Kasman et al, 2009; Kim et al, 2010). They are typically covalently conjugated through the reaction of active groups on the polymer termini to nucleophilic amino acid side chains on the viral surface, such as lysines and cysteines.…”

Section: Strategies To Avoid Neutralization By Humoral Anti-aav Immunmentioning

confidence: 99%

Enhancing the clinical potential of AAV vectors by capsid engineering to evade pre-existing immunity

Bartel¹

2011

Front. Microbio.

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Vectors based on adeno-associated viruses (AAV) have shown considerable promise in both preclinical models and increasingly in clinical trials. However, one formidable challenge is pre-existing immunity due to widespread exposure to numerous AAV variants and serotypes within the human population, which affect efficacy of clinical trials due to the accompanying high levels of anti-capsid neutralizing antibodies. Transient immunosuppression has promise in mitigating cellular and humoral responses induced by vector application in naïve hosts, but cannot overcome the problem that pre-existing neutralizing antibodies pose toward the goal of safe and efficient gene delivery. Shielding of AAV from antibodies, however, may be possible by covalent attachment of polymers to the viral capsid or by encapsulation of vectors inside biomaterials. In addition, there has been considerable progress in using rational mutagenesis, combinatorial libraries, and directed evolution approaches to engineer capsid variants that are not recognized by anti-AAV antibodies generally present in the human population. While additional progress must be made, such strategies, alone or in combination with immunosuppression to avoid de novo induction of antibodies, have strong potential to significantly enhance the clinical efficacy of AAV vectors.

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Abstract: PEGylated adenoviruses are suitable gene delivery vehicles for oral administration.

Cited by 40 publications

References 30 publications

IIIa deleted adenovirus as a single-cycle genome replicating vector

IIIa deleted adenovirus as a single-cycle genome replicating vector

PEGylation as a strategy for improving nanoparticle-based drug and gene delivery

Enhancing the clinical potential of AAV vectors by capsid engineering to evade pre-existing immunity

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