Gene Silencing by siRNA Microhydrogels via Polymeric Nanoscale Condensation

Hong, Cheol Am; Lee, Soo Hyun; Kim, Jee Seon; Park, Ji Won; Bae, Ki Hyun; Mok, Hyejung; Park, Tae Gwan; Lee, Haeshin

doi:10.1021/ja2056984

Cited by 58 publications

(36 citation statements)

References 45 publications

(19 reference statements)

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“…In addition to lipid‐, polymer‐, siRNA conjugate‐ and inorganic systems there are other nano‐and microsystems such as microhydrogels, microneedles, self‐assembled siRNA oligonucleotide nanoparticles and microsponges which exemplify the myriad directions siRNA delivery is currently developing. Furthermore, controlled mixing processes such as microfluidic methods have been developed to achieve consistent quality and reproducibility of siRNA formulations with high yield and uniform size .…”

Section: Resultsmentioning

confidence: 99%

Biomaterials in siRNA Delivery: A Comprehensive Review

Zhang

2016

Adv Healthcare Materials

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With the dearth of effective treatment options for prominent diseases including Ebola and cancer, RNA interference (RNAi), a sequence-specific mechanism for genetic regulation that can silence nearly any gene, holds the promise of unlimited potential in treating illness ever since its discovery in 1999. Given the large size, unstable tertiary structure in physiological conditions and negative charge of small interfering RNAs (siRNAs), the development of safe and effective delivery vehicles is of critical importance in order to drive the widespread use of RNAi therapeutics into clinical settings. Immense amounts of time and billions of dollars have been devoted into the design of novel and diverse delivery strategies, and there are a handful of delivery systems that have been successfully translated into clinic. This review provides an introduction to the in vivo barriers that need to be addressed by siRNA delivery systems. We also discuss the progress up to the most effective and clinically advanced siRNA delivery systems including liposomal, polymeric and siRNA conjugate delivery systems, as well as their design to overcome the challenges.

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Section: Resultsmentioning

confidence: 99%

Biomaterials in siRNA Delivery: A Comprehensive Review

Zhang

2016

Adv Healthcare Materials

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“…For example, endless dumbbell-shaped circular siRNAs [120,121], complexes of PEI and short oligomers of complementary overhang siRNAs (sticky siRNA) [122], linear PEI complexes with several cross-linked siRNAs molecules [123], 3D siRNA microhydrogels [124], RNAi microsponges [125], chimeric packaging RNA (pRNA) derived from the bacteriophage phi29 DNA [126,127], and RNA nanorings functionalized with siRNAs [128,129]. RNAi-aptamers, RNAi attached to cell penetrating peptides, and RNAi CNS-ligand conjugates have been explored for GBM therapy and are discussed in the next sections.…”

Section: Assessing Rnai Delivery For Gbm Treatmentmentioning

confidence: 99%

RNA interference for glioblastoma therapy: Innovation ladder from the bench to clinical trials

2017

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Glioblastoma multiforme (GBM) is the most common and deadliest type of primary brain tumor with a prognosis of 14 months after diagnosis. Current treatment for GBM patients includes “total” tumor resection, temozolomide-based chemotherapy, radiotherapy or a combination of these options. Although, several targeted therapies, gene therapy, and immunotherapy are currently in the clinic and/or in clinical trials, the overall survival of GBM patients has hardly improved over the last two decades. Therefore, novel multitarget modalities are urgently needed. Recently, RNA interference (RNAi) has emerged as a novel strategy for the treatment of most cancers, including GBM. RNAi-based therapies consist of using small RNA oligonucleotides to regulate protein expression at the post-transcriptional level. Despite the therapeutic potential of RNAi molecules, systemic limitations including short circulatory stability and low release into the tumor tissue have halted their progress to the clinic. The effective delivery of RNAi molecules through the blood-brain barrier (BBB) represents an additional challenge. This review focuses on connecting the translational process of RNAi-based therapies from in vitro evidence to pre-clinical studies. We delineate the effect of RNAi in GBM cell lines, describe their effectiveness in glioma mouse models, and compare the proposed drug carriers for the effective transport of RNAi molecules through the BBB to reach the tumor in the brain. Furthermore, we summarize the most important obstacles to overcome before RNAi-based therapy becomes a reality for GBM treatment.

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“…conducted the first attempt to prepare biologically active siRNA-based microhydrogels using sense/antisense complementary hybridization between single-stranded linear and Y-shaped trimeric siRNAs. These siRNA microhydrogels interestingly exhibited super cellular uptake efficiency and gene silencing activity 198.…”

Section: Nanoparticles In Rnai Therapeuticsmentioning

confidence: 99%

Nanoparticle-Mediated Systemic Delivery of siRNA for Treatment of Cancers and Viral Infections

Draz¹,

Fang²,

Zhang³

et al. 2014

Theranostics

199

153

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RNA interference (RNAi) is an endogenous post-transcriptional gene regulatory mechanism, where non-coding, double-stranded RNA molecules interfere with the expression of certain genes in order to silence it. Since its discovery, this phenomenon has evolved as powerful technology to diagnose and treat diseases at cellular and molecular levels. With a lot of attention, short interfering RNA (siRNA) therapeutics has brought a great hope for treatment of various undruggable diseases, including genetic diseases, cancer, and resistant viral infections. However, the challenge of their systemic delivery and on how they are integrated to exhibit the desired properties and functions remains a key bottleneck for realizing its full potential. Nanoparticles are currently well known to exhibit a number of unique properties that could be strategically tailored into new advanced siRNA delivery systems. This review summarizes the various nanoparticulate systems developed so far in the literature for systemic delivery of siRNA, which include silica and silicon-based nanoparticles, metal and metal oxides nanoparticles, carbon nanotubes, graphene, dendrimers, polymers, cyclodextrins, lipids, hydrogels, and semiconductor nanocrystals. Challenges and barriers to the delivery of siRNA and the role of different nanoparticles to surmount these challenges are also included in the review.

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Gene Silencing by siRNA Microhydrogels via Polymeric Nanoscale Condensation

Cited by 58 publications

References 45 publications

Biomaterials in siRNA Delivery: A Comprehensive Review

Biomaterials in siRNA Delivery: A Comprehensive Review

RNA interference for glioblastoma therapy: Innovation ladder from the bench to clinical trials

Nanoparticle-Mediated Systemic Delivery of siRNA for Treatment of Cancers and Viral Infections

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