Bioengineered nanoparticles for <scp>siRNA</scp> delivery

Kozielski, Kristen L.; Tzeng, Stephany Y.; Green, Jordan J.

doi:10.1002/wnan.1233

Cited by 47 publications

(46 citation statements)

References 156 publications

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“…[40] Furthermore, research on PEI modifications has already seen modified PEIs achieve reduced cytotoxicity while maintaining high efficacy. [41] However, in general, PEIs with higher molecular weights and bPEIs typically induce greater cytotoxicity compared to those with lower molecular weights and lPEIs. PEIs are not easily biodegradable which leads to high toxicity, and although more research for PEI modifications to decrease cytotoxicity can be conducted, many researchers are simply exploring and studying other carriers that are associated with lower cytotoxicity.…”

Section: Dendrimersmentioning

confidence: 99%

“…[46] Furthermore, AuNPs are attractive due to their low cytotoxicity. [41] Additionally, AuNP conjugates have been reported to be successful in the topical delivery of siRNAs in vivo. [41,47] …”

Section: Gold Nanoparticlesmentioning

confidence: 99%

“…[41] Additionally, AuNP conjugates have been reported to be successful in the topical delivery of siRNAs in vivo. [41,47] …”

Section: Gold Nanoparticlesmentioning

confidence: 99%

“…As methods of molecular imaging, quantum dots are attractive due to their relatively higher brightness, their smaller chances of photobleaching, and their ease in being detected compared to fluorescent dyes. [41,46] Additionally, because of the tunable emission of quantum dots, they have become attractive to researchers who are studying the delivery of siRNA via these quantum dots into cells and small animals. [63] …”

Section: Mesoporous Silica-based Nanoparticlesmentioning

confidence: 99%

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An Overview of Various Carriers for siRNA Delivery

Marquez¹,

Madu²,

Lü³

2018

Oncomedicine

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RNA interference through the use of short interfering molecules known as short interfering RNA (siRNA) has the potential to greatly advance research in treatments for many diseases because it has the ability to silence the expression of specific genes by helping degrade target mRNA. However, challenges to siRNA delivery have made the development of safe and effective delivery systems paramount in siRNA research. Various types of delivery systems have been proposed and investigated for siRNA delivery and therapy. Although viral vectors have been established to be the most effective in delivering siRNA molecules, they also raise many concerns over biosafety, especially concerning immunogenicity. Therefore, many researchers have begun to investigate and study non-viral vectors. Non-viral vectors are studied because they are typically considered to be safer than viral vectors albeit less efficient as well. The three general non-viral vectors that have been studied for siRNA delivery are lipid-based, non-lipid organic-based, and non-lipid inorganic-based carriers. Within those general parameters of non-viral vector classification are subtypes that are each unique with their own characteristic benefits and downsides. Many of these carriers, as well as even naked siRNA, do have the potential to be modified so that siRNA delivery could be further enhanced with benefits such as greater stability and duration. Researchers still must be wary with alterations as to not interfere with siRNA function. Currently, widespread siRNA therapeutics are still out of reach, but as more advancements in siRNA research including research on their delivery mechanisms are established, the goal of integrating siRNA therapy into the treatment of a multitude of diseases becomes increasingly more of a possibility. Researchers are currently investigating how siRNA can be used to not just treat cancer but ocular and neurodegenerative diseases as well as many others. There are still many obstacles to face and overcome before siRNA therapy can be implemented into the treatment of many diseases, and more research must still be conducted concerning siRNA delivery systems. Many advancements pertaining to siRNA carriers have been made, and many more are likely on their way.

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Section: Dendrimersmentioning

confidence: 99%

Section: Gold Nanoparticlesmentioning

confidence: 99%

“…[41] Additionally, AuNP conjugates have been reported to be successful in the topical delivery of siRNAs in vivo. [41,47] …”

Section: Gold Nanoparticlesmentioning

confidence: 99%

Section: Mesoporous Silica-based Nanoparticlesmentioning

confidence: 99%

See 2 more Smart Citations

An Overview of Various Carriers for siRNA Delivery

Marquez¹,

Madu²,

Lü³

2018

Oncomedicine

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show abstract

“…1–4 However, the high rigidity and low valency of siRNA presents challenges in stable encapsulation, often necessitating large amounts of cationic delivery materials and poor in vivo silencing efficiency. 5–7 To address these challenges, we previously adopted a polymeric form of siRNA, or periodic short hairpin RNA (p-shRNA), whose high valency and flexibility require far less polycationic carrier to condense into stable nanoparticles. 8,9 Generated by rolling circle transcription (RCT) of a dumbbell DNA template, p-shRNA consists of siRNAs linked by short single stranded regions, and can be engineered to possess open ends for improved intracellular processing by Dicer into siRNAs, enhancing silencing efficacy when delivered in vitro with various commercial transfection reagents.…”

mentioning

confidence: 99%

Rationally Designed Polycationic Carriers for Potent Polymeric siRNA-Mediated Gene Silencing

Wang

et al. 2018

ACS Nano

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The delivery of small interfering RNA (siRNA) remains a major hurdle for the clinical translation of RNA interference (RNAi) therapeutics. Due to its low valency and rigid nature, siRNA typically requires high excesses of cationic delivery materials to package it stably and deliver it to the cytoplasm of target cells, resulting in high toxicities and inefficient gene silencing in vivo. To address these challenges, we pair a polymeric form of siRNA, p-shRNA, with optimized biodegradable polycations to form stable complexes that induce far more potent gene silencing than with siRNA complexes. Furthermore, we unveil a set of design rules governing p-shRNA delivery, using degradable polycations containing hydrophobic and stabilizing polyethylene glycol domains that enable both stable condensation and efficient release inside cells. We demonstrate the therapeutic potential of this approach by silencing the oncogene STAT3 in a well-established B16F10 mouse melanoma model to significantly prolong survival. By blending nucleic acid engineering and polymer design, our system provides a potentially translatable platform for RNAi-based therapies.

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Nucleic Acid Delivery from Granular Hydrogels

Kurt

Segura

2021

Adv Healthcare Materials

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Nucleic acid delivery has applications ranging from tissue engineering to vaccine development to infectious disease. Cationic polymer condensed nucleic acids are used with surface‐coated porous scaffolds and are able to promote long‐term gene expression. However, due to surface loading of the scaffold, there is a limit to the amount of nucleic acid that can be loaded, resulting in decreasing expression rate over time. In addition, surface‐coated scaffolds are generally non‐injectable. Here, it is demonstrated that cationic polymer condensed nucleic acids can be effectively loaded into injectable granular hydrogel scaffolds by stabilizing the condensed nucleic acid into a lyophilized powder, loading the powder into a bulk hydrogel, and then fragmenting the loaded hydrogel. The resulting hydrogel microparticles contain non‐aggregated nucleic acid particles, can be annealed post‐injection to result in an injectable microporous hydrogel, and can effectively deliver nucleic acids to embedded cells with a constant expression rate. Due to the nature of granular hydrogels, it is demonstrated that mixtures of loaded and unloaded particles and spatially resolved gene expression can be easily achieved. The ability to express genes long term from an injectable porous hydrogel will further open the applications of nucleic acid delivery.

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Bioengineered nanoparticles for siRNA delivery

Cited by 47 publications

References 156 publications

An Overview of Various Carriers for siRNA Delivery

An Overview of Various Carriers for siRNA Delivery

Rationally Designed Polycationic Carriers for Potent Polymeric siRNA-Mediated Gene Silencing

Nucleic Acid Delivery from Granular Hydrogels

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