Nanomedicine-based delivery strategies for nucleic acid gene inhibitors in inflammatory diseases

Fattal, Elias; Fay, François

doi:10.1016/j.addr.2021.05.019

Cited by 35 publications

(23 citation statements)

References 275 publications

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“…Degradation of siRNA before reaching its cellular destination is a frequently discussed problem [ 73 , 74 ], not least because the nucleotides are exposed to RNases when they enter the bloodstream and therefore need to be protected. Aside from ensuring a constant release of siRNA, carriers also shield siRNA from molecules responsible for their degradation, as has already been shown for PAMAM dendrimers [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Analyzing siRNA Concentration, Complexation and Stability in Cationic Dendriplexes by Stem-Loop Reverse Transcription-qPCR

et al. 2022

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RNA interference (RNAi) is a powerful therapeutic approach for messenger RNA (mRNA) level regulation in human cells. RNAi can be triggered by small interfering RNAs (siRNAs) which are delivered by non-viral carriers, e.g., dendriplexes. siRNA quantification inside carriers is essential in drug delivery system development. However, current siRNA measuring methods either are not very sensitive, only semi-quantitative or not specific towards intact target siRNA sequences. We present a novel reverse transcription real-time PCR (RT-qPCR)-based application for siRNA quantification in drug formulations. It enables specific and highly sensitive quantification of released, uncomplexed target siRNA and thus also indirect assessment of siRNA stability and concentration inside dendriplexes. We show that comparison with a dilution series allows for siRNA quantification, exclusively measuring intact target sequences. The limit of detection (LOD) was 4.2 pM (±0.2 pM) and the limit of quantification (LOQ) 77.8 pM (±13.4 pM) for uncomplexed siRNA. LOD and LOQ of dendriplex samples were 31.6 pM (±0 pM) and 44.4 pM (±9.0 pM), respectively. Unspecific non-target siRNA sequences did not decrease quantification accuracy when present in samples. As an example of use, we assessed siRNA complexation inside dendriplexes with varying nitrogen-to-phosphate ratios. Further, protection of siRNA inside dendriplexes from RNase A degradation was quantitatively compared to degradation of uncomplexed siRNA. This novel application for quantification of siRNA in drug delivery systems is an important tool for the development of new siRNA-based drugs and quality checks including drug stability measurements.

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Section: Discussionmentioning

confidence: 99%

Analyzing siRNA Concentration, Complexation and Stability in Cationic Dendriplexes by Stem-Loop Reverse Transcription-qPCR

et al. 2022

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“…[ 99 , 100 ] The sequences and concentrations of nucleic acids have been strongly demonstrated to be implicated in many disorders‐related diseases. [ 101 , 102 ] Therefore, the detection of nucleic acids is extremely significant. For example, viruses, the collection of nucleic acids, can infect cells and kill the host cells and cause huge damage to organism.…”

Section: Dna Walkers‐based Biosensorsmentioning

confidence: 99%

DNA Walkers for Biosensing Development

et al. 2022

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The ability to design nanostructures with arbitrary shapes and controllable motions has made DNA nanomaterials used widely to construct diverse nanomachines with various structures and functions. The DNA nanostructures exhibit excellent properties, including programmability, stability, biocompatibility, and can be modified with different functional groups. Among these nanoscale architectures, DNA walker is one of the most popular nanodevices with ingenious design and flexible function. In the past several years, DNA walkers have made amazing progress ranging from structural design to biological applications including constructing biosensors for the detection of cancer‐associated biomarkers. In this review, the key driving forces of DNA walkers are first summarized. Then, the DNA walkers with different numbers of legs are introduced. Furthermore, the biosensing applications of DNA walkers including the detection‐ of nucleic acids, proteins, ions, and bacteria are summarized. Finally, the new frontiers and opportunities for developing DNA walker‐based biosensors are discussed.

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“…For intracellular delivery purposes, nanomaterials including the lipid nanoparticles, (naturally derived and fully synthetic) polymeric nanoparticles, and inorganic nanoparticles ( e.g. , gold nanoparticles, carbon- and silica-based nanoparticles, and iron oxide nanoparticles) have been intensively studied 6 , 7 , 8 , 9 , 10 , 11 . Each delivery system has its own advantages and disadvantages.…”

Section: Introductionmentioning

confidence: 99%

Tailoring combinatorial lipid nanoparticles for intracellular delivery of nucleic acids, proteins, and drugs

Yang

et al. 2022

Acta Pharmaceutica Sinica B

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Nanomedicine-based delivery strategies for nucleic acid gene inhibitors in inflammatory diseases

Cited by 35 publications

References 275 publications

Analyzing siRNA Concentration, Complexation and Stability in Cationic Dendriplexes by Stem-Loop Reverse Transcription-qPCR

Analyzing siRNA Concentration, Complexation and Stability in Cationic Dendriplexes by Stem-Loop Reverse Transcription-qPCR

DNA Walkers for Biosensing Development

Tailoring combinatorial lipid nanoparticles for intracellular delivery of nucleic acids, proteins, and drugs

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