Evolving Lessons on Nanomaterial-Coated Viral Vectors for Local and Systemic Gene Therapy

Kasala, Dayananda; Yoon, A-Rum; Hong, Jin; Kim, Sung Wan; Yun, Chae Ok

doi:10.2217/nnm-2016-0060

Cited by 34 publications

(20 citation statements)

References 156 publications

(174 reference statements)

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“…Another limitation of oAd is its poor intratumoral retention and nonspecific shedding to surrounding normal tissues [14,22]. A decent fraction of intratumorally administered oAd does not internalize into tumor cells and shedding of virions into the bloodstream eventually leads to nonspecific sequestration of viruses into normal tissues, thus leading to adverse side effects and insufficient therapeutic efficacy.…”

Section: Introductionmentioning

confidence: 99%

“…Further, enhanced cellular internalization of oAd by nanomaterials can improve viral replication and elevate therapeutic transgene expression levels by oAd in cancer cells, thus greatly improving the therapeutic effect of armed oAds [26,28]. Alternatively, gel-or magnetic nanoparticle (MNP)based delivery of oAd have been shown to improve intratumoral retention of virus and limit the nonspecific shedding [14]. Although there are limited number of literature available, the nanomaterial-based local delivery platform has also been explored to address the limitations of other oncolytic viruses through similar principles as mentioned above [29].…”

Section: Introductionmentioning

confidence: 99%

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Overcoming the limitations of locally administered oncolytic virotherapy

Hong

Yun

2019

BMC biomed eng

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Adenovirus (Ad) has been most extensively evaluated gene transfer vector in clinical trials due to facile production in high viral titer, highly efficient transduction, and proven safety record. Similarly, an oncolytic Ad, which replicates selectively in cancer cells through genetic modifications, is actively being evaluated in various phases of clinical trials as a promising next generation therapeutic against cancer. Most of these trials with oncolytic Ads to date have employed intratumoral injection as the standard administration route. Although these locally administered oncolytic Ads have shown promising outcomes, the therapeutic efficacy is not yet optimal due to poor intratumoral virion retention, nonspecific shedding of virion to normal organs, variable infection efficacy due to heterogeneity of tumor cells, adverse antiviral immune response, and short biological activity of oncolytic viruses in situ. These inherent problems associated with locally administered Ad also holds true for other oncolytic viral vectors. Thus, this review will aim to discuss various nanomaterial-based delivery strategies to improve the intratumoral administration efficacy of oncolytic Ad as well as other types of oncolytic viruses.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Overcoming the limitations of locally administered oncolytic virotherapy

Hong

Yun

2019

BMC biomed eng

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“…However, the use of oncolytic viruses is partially limited because of their immunogenicity and the pre-existing humoral immunity in the general population [ 30 , 31 , 32 ] or the humoral immunity elicited by the first virus administration in repeated doses, which is able to neutralize their infectivity. As only systemic therapeutics can target both primary and secondary tumors, recent studies have focused on the development of carriers for oncolytic adenoviruses delivery to tumor tissues via a systemic route [ 33 ], such as hybrid vector systems generated by complexing oncolytic Ad with nanoparticles [ 34 ]. Employing plasmids that encode oncolytic viruses instead of using viruses themselves could mediate a conditional replication of the virus only in cancer cells but avoid their undesired immune effect [ 35 ].…”

Section: Introductionmentioning

confidence: 99%

Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome

Sendra

Miguel

et al. 2020

Nanomaterials

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Oncolytic adenoviruses are a therapeutic alternative to treat cancer based on their ability to replicate selectively in tumor cells. However, their use is limited mainly by the neutralizing antibody (Nab) immune response that prevents repeated dosing. An alternative to facilitate the DNA access to the tumor even in the presence of anti-viral Nabs could be gold nanoparticles able to transfer DNA molecules. However, the ability of these nanoparticles to carry large DNA molecules, such as an oncolytic adenovirus genome, has not been studied. In this work, gold nanoparticles were functionalized with different amounts of polyethylenimine to transfer in a safe and efficient manner a large oncolytic virus genome. Their transfer efficacy and final effect of the oncolytic virus in cancer cells are studied. For each synthesized nanoparticle, (a) DNA loading capacity, (b) complex size, (c) DNA protection ability, (d) transfection efficacy and (e) cytotoxic effect were studied. We observed that small gold nanoparticles (70–80 nm in diameter) protected DNA against nucleases and were able to transfect the ICOVIR-15 oncolytic virus genome encoded in pLR1 plasmid. In the present work, efficient transgene RNA expression, luciferase activity and viral cytopathic effect on cancer cells are reported. These results suggest gold nanoparticles to be an efficient and safe vector for oncolytic adenovirus genome transfer.

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“…Recently, the US Food & Drug Administration approved the first gene therapy that uses viral vectors to accomplish gene transduction (Russell et al, ). Although the currently used viral vectors display organ tropism, meaning they get expressed only in certain tissues, despite being administered systemically (Zincarelli, Soltys, Rengo, & Rabinowitz, ), local delivery of viral vectors to specific tissues can help limit the immune response by requiring lower doses than systemic injections, and local delivery can limit off‐target transduction (Kasala, Yoon, Hong, Kim, & Yun, ; Katz, Fargnoli, Pritchette, & Bridges, ). Injection of viral vectors into muscular or cardiac tissue achieves local virus delivery; however, transduction is limited to the area immediately surrounding the injection, thus requiring repeated injections to transduce a larger area.…”

Section: Introductionmentioning

confidence: 99%

Adhesive thermosensitive gels for local delivery of viral vectors

Caronia

Sorensen

Leslie

et al. 2019

Biotech & Bioengineering

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Local delivery of viral vectors can enhance the efficacy of therapies by selectively affecting necessary tissues and reducing the required vector dose. Pluronic F127 is a thermosensitive polymer that undergoes a solution-gelation (sol-gel) transition as temperature increases and can deliver vectors without damaging them. While pluronics can be spread over large areas, such as the surface of an organ, before gelation, they lack sufficient adhesivity to remain attached to some tissues, such as the surface of the heart or mucosal surfaces. Here, we utilized blends of pluronic F127 and polycarbophil (PCB), a mucoadhesive agent, to provide the necessary adhesivity for local delivery of viral vectors to the cardiac muscle. The effects of PCB concentration on adhesive properties, sol-gel temperature transition and cytocompatibility were evaluated. Rheological studies showed that PCB decreased the sol-gel transition temperature at concentrations >1% and increased the adhesive properties of the gel. Furthermore, these gels were able to deliver viral vectors and transduce cells in vitro and in vivo in a neonatal mouse apical resection model. These gels could be a useful platform for delivering viral vectors over the surface of organs where increased adhesivity is required. K E Y W O R D S adhesion, pluronic F127, polycarbophil, solution-gelation transition, viral vector delivery

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Evolving Lessons on Nanomaterial-Coated Viral Vectors for Local and Systemic Gene Therapy

Cited by 34 publications

References 156 publications

Overcoming the limitations of locally administered oncolytic virotherapy

Overcoming the limitations of locally administered oncolytic virotherapy

Gold Nanoparticle-Assisted Virus Formation by Means of the Delivery of an Oncolytic Adenovirus Genome

Adhesive thermosensitive gels for local delivery of viral vectors

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