Targeted Adenoviral Vectors I

Dmitriev, Igor; Kaliberov, Sergey A.

doi:10.1016/b978-0-12-800276-6.00009-7

Cited by 3 publications

(1 citation statement)

References 135 publications

(121 reference statements)

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“…Targeting strategies employing manipulation of the HAdV genome among others include peptide incorporation to the HI loop and C-terminus of the knob domain, serotype chimerism, fiber/knob replacement, and combinatorial approaches-chimeric HAdV composed of fiber/knob domains from alternative serotypes, fiber-xenotyped HAdV vectors displaying fibers from nonhuman AdV species, and knobless HAdV fiber-fibritin fusion [6]. Genetic incorporation of peptides into the HVR (hypervariable region) of hexon and C-terminus of the pIX are also possible [27].…”

Section: Role Of the Fiber Receptors' Interactions In Human Adenovirus Cell Entrymentioning

confidence: 99%

The Revolving Door of Adenovirus Cell Entry: Not All Pathways Are Equal

et al. 2021

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Adenoviruses represent exceptional candidates for wide-ranging therapeutic applications, from vectors for gene therapy to oncolytics for cancer treatments. The first ever commercial gene therapy medicine was based on a recombinant adenovirus vector, while most recently, adenoviral vectors have proven critical as vaccine platforms in effectively controlling the global coronavirus pandemic. Here, we discuss factors involved in adenovirus cell binding, entry, and trafficking; how they influence efficiency of adenovirus-based vectors; and how they can be manipulated to enhance efficacy of genetically modified adenoviral variants. We focus particularly on endocytosis and how different adenovirus serotypes employ different endocytic pathways to gain cell entry, and thus, have different intracellular trafficking pathways that subsequently trigger different host antiviral responses. In the context of gene therapy, the final goal of the adenovirus vector is to efficiently deliver therapeutic transgenes into the target cell nucleus, thus allowing its functional expression. Aberrant or inefficient endocytosis can impede this goal, therefore, it should be considered when designing and constructing adenovirus-based vectors.

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Section: Role Of the Fiber Receptors' Interactions In Human Adenovirus Cell Entrymentioning

confidence: 99%

The Revolving Door of Adenovirus Cell Entry: Not All Pathways Are Equal

et al. 2021

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In vivo editing of the pan-endothelium by immunity evading simian adenoviral vector

Lőrincz¹,

Alvarez²,

Walkey³

et al. 2023

Biomedicine & Pharmacotherapy

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Efficient Genome Editing Achieved via Plug-and-Play Adenovirus Piggyback Transport of Cas9/gRNA Complex on Viral Capsid Surface

Dmitriev

et al. 2022

ACS Nano

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The capacity to efficiently deliver the gene-editing enzyme complex to target cells is favored over other forms of gene delivery as it offers one-time hit-and-run gene editing, thus improving precision and safety and reducing potential immunogenicity against edited cells in clinical applications. Here we performed a proof-of-mechanism study and demonstrated that a simian adenoviral vector for DNA delivery can be repurposed as a robust intracellular delivery platform for a functional Cas9/guide RNA (gRNA) complex to recipient cells. In this system, the clinically relevant adenovirus was genetically engineered with a plug-and-display technology based on SpyTag003/SpyCatcher003 coupling chemistry. Under physiological conditions, an off-the-shelf mixture of viral vector with SpyTag003 incorporated into surface capsid proteins and Cas9 fused with SpyCatcher003 led to a rapid titration reaction yielding adenovirus carrying Cas9SpyCatcher003 on the virus surface. The Cas9 fusion protein-conjugated viruses in the presence of a reporter gRNA delivered gene-editing functions to cells with an efficiency comparable to that of a commercial CRISPR/Cas9 transfection reagent. Our data fully validate the adenoviral “piggyback” approach to deliver an intracellularly acting enzyme cargo and, thus, warrant the prospect of engineering tissue-targeted adenovirus carrying Cas9/gRNA for in vivo gene editing.

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Targeted Adenoviral Vectors I

Cited by 3 publications

References 135 publications

The Revolving Door of Adenovirus Cell Entry: Not All Pathways Are Equal

The Revolving Door of Adenovirus Cell Entry: Not All Pathways Are Equal

In vivo editing of the pan-endothelium by immunity evading simian adenoviral vector

Efficient Genome Editing Achieved via Plug-and-Play Adenovirus Piggyback Transport of Cas9/gRNA Complex on Viral Capsid Surface

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