Effective PEI-mediated delivery of CRISPR-Cas9 complex for targeted gene therapy

Ryu, Nari; Kim, Mina; Park, Dongsik; Lee, Byeonghyeon; Kim, Ye‐Ri; Kim, Kyung‐Hee; Baek, Jeong‐In; Kim, Won Jong; Lee, Kyu-Yup; Kim, Un-Kyung

doi:10.1016/j.nano.2018.06.009

Cited by 77 publications

(49 citation statements)

References 34 publications

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“…As intravenous injection is the most common method to administer therapeutics, it is critical to ensure that the nanoparticle reaches its targeted destination. Although research reported that encapsulated DNA into particles have modified their nanoparticles to be less toxic, have higher cellular uptake, or increase payload [41,43,74], it still have a limitation of off target delivery which causes systemic effects [75,76]. For this reason, we investigated two endothelial cell specific antibodies, anti-EGFL7 and anti-Tie2+Tie1, on their ability to enhance cellular uptake in static and dynamic environments.…”

Section: Discussionmentioning

confidence: 99%

“…Cationic polymers have been used extensively to deliver genetic materials as DNA condenses quickly on the oppositely charges positive polymer. These polymers can be synthetic or organic and usually include polyethylenimine [40,41], polyamidoamine [42,43], chitosan [44,45], and cationic proteins [46] or peptides. However, the drawbacks of these highly positively charged polymers are mainly due to its toxicity [32,33] and often require extensive surface modifications to alleviate those effects [33].…”

Section: Introductionmentioning

confidence: 99%

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Notch Intracellular Domain Plasmid Delivery via Poly(lactic-co-glycolic acid) Nanoparticles to Upregulate Notch Signaling

Chintapula

et al. 2021

Preprint

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Notch signaling is a highly conserved signaling system that is required for embryonic development and regeneration of organs. When the signal is lost, maldevelopment occurs and leads to a lethal state. Liposomes and retroviruses are most commonly used to deliver genetic material to cells. However, there are many drawbacks to these systems such as increased toxicity, nonspecific delivery, short half-life, and stability after formulation. We utilized the negatively charged and FDA approved polymer poly(lactic-co-glycolic acid) to encapsulate Notch Intracellular Domaincontaining plasmid in nanoparticles. In this study, we show that primary human umbilical vein endothelial cells readily uptake the nanoparticles with and without specific antibody targets. We demonstrated that our nanoparticles also are nontoxic, stable over time, and compatible with blood. We also determined that we can successfully transfect primary human umbilical vein endothelial cells (HUVECs) with our nanoparticles in static and dynamic environments. Lastly, we elucidated that our transfection upregulates the downstream genes of Notch signaling, indicating that the payload was viable and successfully altered the genetic downstream effects.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Notch Intracellular Domain Plasmid Delivery via Poly(lactic-co-glycolic acid) Nanoparticles to Upregulate Notch Signaling

Chintapula

et al. 2021

Preprint

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“…In order to address these challenges, transient delivery of sgRNA along with the Cas9 mRNA or Cas9 protein has been achieved using non-viral methods such as electroporation, 15,16 hydrodynamic injection, 17 microinjection, 18 lipids, [19][20][21][22] peptides, [23][24][25][26][27][28] polyethylenimine in combination with other agents such as DNA nanoclew, graphene oxide, cholesterol, [29][30][31] gold nanoparticles and other nanostructures, [32][33][34][35][36][37][38] extracellular vesicles, [39][40][41][42] virus-like particles, 43 and biolistic delivery in plants. 44,45 Apart from these methods, many hybrid frameworks have also been used to deliver CRISPR/Cas9.…”

Section: Introductionmentioning

confidence: 99%

Non-viral delivery of CRISPR/Cas9 complex using CRISPR-GPS nanocomplexes

Jain

Rananaware

et al. 2019

Nanoscale

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“…8 For transfection and optimal drug delivery vehicle, 25 kDa-branched PEI is considered as a gold standard, however, with increasing molecular weight, the cytotoxicity toward cells also increases. 12…”

Section: Introductionmentioning

confidence: 99%

Functionally modified magnetic nanoparticles for effective siRNA delivery to prostate cancer cells in vitro

et al. 2019

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Different types of siRNA delivery vehicles including nanoparticles have been synthesized and utilized for prostate cancer gene therapy. However, one of the most common limitations being faced is the toxicity of cationic polymers toward the cells. In the current study, magnetic nanoparticles were prepared and conjugated with cationic polymer, polyethylenimine. Then polyethylene glycol was conjugated with polyethylenimine to improve the biocompatibility of nanoparticles. The transmission electron microscopy size of nanoparticles was found to be 15.82 (±9.07) nm, while hydrodynamic size was about 79.20 (±0.68) nm. Zeta potential analysis of polyethylenimine and polyethylene glycol-coated nanoparticles was +31.4 (±0.62) and +5.65 (±0.76) mV, respectively. Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance confirmed the presence of polyethylene glycol and polyethylenimine polymers in magnetic nanoparticles. Cell viability test in mouse fibroblast NIH 3T3 and prostate cancer PC3 cells showed an increased in biocompatibility of functionally modified polyethylene glycol–polyethylenimine–Fe3O4 nanoparticles. siRNA targeting a disintegrin and metalloproteinase 10 (ADAM10) was successfully loaded into the polyethylene glycol–polyethylenimine–Fe3O4 nanoparticles and delivered to PC3 cells. The results clearly demonstrated a significant decrease in cell viability, which increased within a certain siRNA concentration. The inhibitory concentration (IC50) value for ADAM10 siRNA was calculated to be 15.83 nM after 72 h. Confocal microscopy confirmed the delivery of siRNA-loaded nanoparticles intracellularly to the tumor cells cytosol. This magnetic system can be used as a powerful platform to inhibit cancer cells progression.

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Effective PEI-mediated delivery of CRISPR-Cas9 complex for targeted gene therapy

Cited by 77 publications

References 34 publications

Notch Intracellular Domain Plasmid Delivery via Poly(lactic-co-glycolic acid) Nanoparticles to Upregulate Notch Signaling

Notch Intracellular Domain Plasmid Delivery via Poly(lactic-co-glycolic acid) Nanoparticles to Upregulate Notch Signaling

Non-viral delivery of CRISPR/Cas9 complex using CRISPR-GPS nanocomplexes

Functionally modified magnetic nanoparticles for effective siRNA delivery to prostate cancer cells in vitro

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