A flexible microneedle array as low-voltage electroporation electrodes for in vivo DNA and siRNA delivery

Lab on a Chip ◽  
2014 ◽  
Vol 14 (20) ◽  
pp. 4093-4102 ◽  
Author(s):  
Zewen Wei ◽  
Shuquan Zheng ◽  
Renxin Wang ◽  
Xiangli Bu ◽  
Huailei Ma ◽  
...  

A flexible microneedle array electrode chip for low-voltage electroporation with good tissue adaptation, efficient nucleic acid delivery, and minimum damage.

Polymers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1034 ◽  
Author(s):  
Shuqin Han ◽  
Tsogzolmaa Ganbold ◽  
Qingming Bao ◽  
Takashi Yoshida ◽  
Huricha Baigude

Sugars containing cationic polymers are potential carriers for in vitro and in vivo nucleic acid delivery. Monosaccharides such as glucose and galactose have been chemically conjugated to various materials of synergistic poly-lysine dendrimer systems for efficient and biocompatible delivery of short interfering RNA (siRNA). The synergistic dendrimers, which contain lipid conjugated glucose terminalized lysine dendrimers, have significantly lower adverse impact on cells while maintaining efficient cellular entry. Moreover, the synergistic dendrimers complexed to siRNA induced RNA interference (RNAi) in the cells and profoundly knocked down green fluorescence protein (GFP) as well as the endogenously expressing disease related gene Plk1. The new synergic dendrimers may be promising system for biocompatible and efficient siRNA delivery.


2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi104-vi105
Author(s):  
Akanksha Mahajan ◽  
Lisa Hurley ◽  
Serena Tommasini-Ghelfi ◽  
Corey Dussold ◽  
Alexander Stegh ◽  
...  

Abstract The Stimulator of Interferon Genes (STING) pathway represents a major innate immune sensing mechanism for tumor-derived DNA. Modified cyclic dinucleotides (CDNs) that mimic the endogenous STING ligand cGAMP are currently being explored in patients with solid tumors that are amenable to intratumoral delivery. Inadequate bioavailability and insufficient lipophilicity are limiting factors for clinical CDN development, in particular when consideration is given to systemic administration approaches. We have shown that the formulation of oligonucleotides into Spherical Nucleic Acid (SNA) nanostructures, i.e.,the presentation of oligonucleotides at high density on the surface of nanoparticle cores, lead to biochemical and biological properties that are radically different from those of linear oligonucleotides. First-generation brain-penetrant siRNA-based SNAs (NCT03020017, recurrent GBM) have recently completed early clinical trials. Here, we report the development of a STING-agonistic immunotherapy by targeting cGAS, the sensor of cytosolic dsDNA upstream of STING, with SNAs presenting dsDNA at high surface density. The strategy of using SNAs exploits the ability of cGAS to raise STING responses by delivering dsDNA and inducing the catalytic production of endogenous CDNs. SNA nanostructures carrying a 45bp IFN-simulating dsDNA oligonucleotide, the most commonly used and widely characterized cGAS activator, potently activated the cGAS-STING pathway in vitro and in vivo. In a poorly immunogenic and highly aggressive syngeneic mouse glioma model, in which tumours were well-established, only one dose of intranasal treatment with STING-SNAs decelerated tumour growth, improved survival and importantly, was well-tolerated. Our use of SNAs addresses the challenges of nucleic acid delivery to intracranial tumor sites via intranasal route, exploits the binding of dsDNA molecules on the SNA surface to enhance the formation of a dimeric cGAS:DNA complex and establishes cGAS-agonistic SNAs as a novel class of immune-stimulatory modalities for triggering innate immune responses against tumor.


2012 ◽  
Vol 7 (6) ◽  
pp. 389-393 ◽  
Author(s):  
Hyukjin Lee ◽  
Abigail K. R. Lytton-Jean ◽  
Yi Chen ◽  
Kevin T. Love ◽  
Angela I. Park ◽  
...  

ChemBioChem ◽  
2016 ◽  
Vol 17 (18) ◽  
pp. 1771-1783 ◽  
Author(s):  
Philippe Pierrat ◽  
Anne Casset ◽  
Pascal Didier ◽  
Dimitri Kereselidze ◽  
Marie Lux ◽  
...  

Vaccine ◽  
2010 ◽  
Vol 28 (38) ◽  
pp. 6176-6182 ◽  
Author(s):  
Mohan Karkada ◽  
Genevieve M. Weir ◽  
Tara Quinton ◽  
Antar Fuentes-Ortega ◽  
Marc Mansour

Nano Letters ◽  
2018 ◽  
Vol 18 (3) ◽  
pp. 2148-2157 ◽  
Author(s):  
Kalina Paunovska ◽  
Cory D. Sago ◽  
Christopher M. Monaco ◽  
William H. Hudson ◽  
Marielena Gamboa Castro ◽  
...  

2021 ◽  
Vol 20 ◽  
pp. S277
Author(s):  
A. Piotrowski-Daspit ◽  
L. Bracaglia ◽  
C. Barone ◽  
R. Nguyen ◽  
P. Glazer ◽  
...  

2012 ◽  
Vol 23 (21) ◽  
pp. 2691-2699 ◽  
Author(s):  
Jing Chang ◽  
Xianghui Xu ◽  
Haiping Li ◽  
Yeting Jian ◽  
Gang Wang ◽  
...  

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