Nonviral Delivery Systems for Cancer Gene Therapy: Strategies and Challenges

Shim, Gayong; Kim, Dong-Yoon; Le, Quoc‐Viet; Park, Gyu Thae; Kwon, Taek-Hyun; Oh, Yu‐Kyoung

doi:10.2174/1566523218666180119121949

Cited by 51 publications

(35 citation statements)

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“…Gene therapy has been regarded as a new opportunity to satisfy the needs in treatment of cancer (Das et al, 2015). With the advancement in RNA biology, gene therapies not only introduce the exogenous genes by DNA but also change the gene expression at the mRNA level through by virtue of short interfering RNAs (siRNAs), miRNAs and antisense oligonucleotides (ASOs) (Shim et al, 2018). Recently, Clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9 (CRISPR-Cas9) also opens a new avenue in gene therapy to correct the mutations of cancer (Karimian et al, 2019).…”

Section: Gene Therapymentioning

confidence: 99%

Emerging and Innovative Theranostic Approaches for Mesoporous Silica Nanoparticles in Hepatocellular Carcinoma: Current Status and Advances

Tao

Wang

2020

Front. Bioeng. Biotechnol.

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Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal solid cancers globally. To improve diagnosis sensitivities and treatment efficacies, the development of new theranostic nanoplatforms for efficient HCC management is urgently needed. In the past decade, mesoporous silica nanoparticles (MSNs) with tailored structure, large surface area, high agents loading volume, abundant chemistry functionality, acceptable biocompatibility have received more and more attention in HCC theranostic. This review outlines the recent advances in MSNs-based systems for HCC therapy and diagnosis. The multifunctional hybrid nanostructures that have both of therapy and diagnosis abilities are highlighted. And the precision delivery strategies of MSNs in HCC are also discussed. Final, we conclude with our personal perspectives on the future development and challenges of MSNs.

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Section: Gene Therapymentioning

confidence: 99%

Emerging and Innovative Theranostic Approaches for Mesoporous Silica Nanoparticles in Hepatocellular Carcinoma: Current Status and Advances

Tao

Wang

2020

Front. Bioeng. Biotechnol.

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“…However, non-viral vectors have shown lower transfection efficiencies compared to viral vectors, which have spurred researchers to optimize their design [4]. Non-viral vectors can be categorized into lipids, cationic polymers, peptides, nucleic acid, and inorganic nanoparticles [4,18].…”

Section: Introductionmentioning

confidence: 99%

PEGylated Amine-Functionalized Poly(ε-caprolactone) for the Delivery of Plasmid DNA

et al. 2020

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As a promising strategy for the treatment of various diseases, gene therapy has attracted increasing attention over the past decade. Among various gene delivery approaches, non-viral vectors made of synthetic biomaterials have shown significant potential. Due to their synthetic nature, non-viral vectors can have tunable structures and properties by using various building units. In particular, they can offer advantages over viral vectors with respect to biosafety and cytotoxicity. In this study, a well-defined poly(ethylene glycol)-block-poly(α-(propylthio-N,N-diethylethanamine hydrochloride)-ε-caprolactone) diblock polymer (PEG-b-CPCL) with one poly(ethylene glycol) (PEG) block and one tertiary amine-functionalized cationic poly(ε-caprolactone) (CPCL) block, as a novel non-viral vector in the delivery of plasmid DNA (pDNA), was synthesized and studied. Despite having a degradable polymeric structure, the polymer showed remarkable hydrolytic stability over multiple weeks. The optimal ratio of the polymer to pDNA for nanocomplex formation, pDNA release from the nanocomplex with the presence of heparin, and serum stability of the nanocomplex were probed through gel electrophoresis. Nanostructure of the nanocomplexes was characterized by DLS and TEM imaging. Relative to CPCL homopolymers, PEG-b-CPCL led to better solubility over a wide range of pH. Overall, this work demonstrates that PEG-b-CPCL possesses a range of valuable properties as a promising synthetic vector for pDNA delivery.

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“…Third, plasmids are relatively inexpensive to produce at the research and industrial scale and are more stable compared to viruses 1516 . The efficiency of in vivo DNA delivery has improved significantly as a result of recent advancements in liposome chemistry and nanoparticles, but is still not as efficient as viruses in many cases [17][18][19] . Thus, repeat dosing or increased dose levels have been attempted but these strategies can incur greater costs, risk of side effects, and sacrifice patient convenience.…”

Section: Introductionmentioning

confidence: 99%

High-Throughput 5’ UTR Engineering for Enhanced Protein Production in Non-Viral Gene Therapies

Cao

Novoa

Zhang

et al. 2020

Preprint

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Despite significant clinical progress in cell and gene therapies, maximizing protein expression in order to enhance potency remains a major challenge. One approach to increase protein expression is by optimizing translation through the engineering of 5’ untranslated regions (5’ UTRs). Here, we developed a high-throughput strategy to design, screen, and optimize novel 5’UTRs that enhance protein expression from a strong human cytomegalovirus (CMV) promoter. We first identified naturally occurring 5’ UTRs with high translation efficiencies and used this information with in silico genetic algorithms to generate synthetic 5’ UTRs. A total of ∼12,000 5’ UTRs were then screened using a recombinase-mediated integration strategy that greatly enhances the sensitivity of high-throughput screens by eliminating copy number and position effects that limit lentiviral approaches. Using this approach, we identified three synthetic 5’ UTRs that outperformed commonly used non-viral gene therapy plasmids in expressing protein payloads. Furthermore, combinatorial assembly of these 5’ UTRs enabled even higher protein expression than obtained with each individual 5’ UTR. In summary, we demonstrate that high-throughput screening of 5’ UTR libraries with recombinase-mediated integration can identify genetic elements that enhance protein expression, which should have numerous applications for engineered cell and gene therapies.

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Nonviral Delivery Systems for Cancer Gene Therapy: Strategies and Challenges

Cited by 51 publications

References 0 publications

Emerging and Innovative Theranostic Approaches for Mesoporous Silica Nanoparticles in Hepatocellular Carcinoma: Current Status and Advances

Emerging and Innovative Theranostic Approaches for Mesoporous Silica Nanoparticles in Hepatocellular Carcinoma: Current Status and Advances

PEGylated Amine-Functionalized Poly(ε-caprolactone) for the Delivery of Plasmid DNA

High-Throughput 5’ UTR Engineering for Enhanced Protein Production in Non-Viral Gene Therapies

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