Fighting against kidney diseases with small interfering RNA: opportunities and challenges

Yang, Cheng; Zhang, Chao; Zhao, Zitong; Zhu, Tongyu; Yang, Bin

doi:10.1186/s12967-015-0387-2

Cited by 25 publications

(22 citation statements)

References 81 publications

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“…The main goals of siRNA chemical modifications are to extend the half-life and to increase cellular uptake of the siRNA molecule. [74] Research has already established that modifying siRNAs with locked nucleic acids can extend its half-life to 90 hours without triggering severely negative effects, implying that RNAi machinery can tolerate a moderate amount of modifications to siRNA. Furthermore, to protect against siRNA degradation via nucleases, the backbone of the siRNA molecule can be altered.…”

Section: Sirna and Carrier Modificationsmentioning

confidence: 99%

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: Sirna and Carrier Modificationsmentioning

confidence: 99%

An Overview of Various Carriers for siRNA Delivery

Marquez¹,

Madu²,

Lü³

2018

Oncomedicine

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“…The direct use of naked siRNA is limited to local delivery and to specific sites such as the eye, nose and lungs and systemic application of siRNA therapeutics requires the use of safe and efficient delivery systems, including direct chemical modification of siRNA and/or optimization of delivery systems (ex: liposomal formulations, nanoparticle conjugation and antibodies that target cellular moieties) [147].…”

Section: Chemical Modifications Of Nucleic Acidsmentioning

confidence: 99%

Lipid-based Nanocarriers for siRNA Delivery: Challenges, Strategies and the Lessons Learned from the DODAX: MO Liposomal System

Oliveira

Fernandes

Gonçalves

et al. 2018

CDT

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The possibility of using the RNA interference (RNAi) mechanisms in gene therapy was one of the scientific breakthroughs of the last century. Despite the extraordinary therapeutic potential of this approach, the need for an efficient gene carrier is hampering the translation of the RNAi technology to the clinical setting. Although a diversity of nanocarriers has been described, liposomes continue to be one of the most attractive siRNA vehicles due to their relatively low toxicity, facilitated siRNA complexation, high transfection efficiency and enhanced pharmacokinetic properties. </P><P> This review focuses on RNAi as a therapeutic approach, the challenges to its application, namely the nucleic acids’ delivery process, and current strategies to improve therapeutic efficacy. Additionally, lipid-based nanocarriers are described, and lessons learned from the relation between biophysical properties and biological performance of the dioctadecyldimethylammonium:monoolein (DODAX: MO) system are explored. </P><P> Liposomes show great potential as siRNA delivery systems, being safe nanocarriers to protect nucleic acids in circulation, extend their half-life time, target specific cells and reduce off-target effects. Nevertheless, several issues related to delivery must be overcome before RNAi therapies reach their full potential, namely target-cell specificity and endosomal escape. Understanding the relationship between biophysical properties and biological performance is an essential step in the gene therapy field.

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“…31 The stability of siRNA/DMAPA-chems complexes (N/P =100) was evaluated in 25% FBS ( Figure 3B). Naked siRNA control group was totally degraded within 24 hours of cultivation, while the migration of siRNA was still observed after siRNA/DMAPA-chems complexes treated with heparin solution were cultivated in 25% FBS.…”

Section: Agarose Gel Electrophoresis and Stability Analysismentioning

confidence: 99%

Efficient delivery of Notch1 siRNA to SKOV3 cells by cationic cholesterol derivative-based liposome

Zhao¹,

Zhang²,

Feng³

et al. 2016

IJN

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A novel cationic cholesterol derivative-based small interfering RNA (siRNA) interference strategy was suggested to inhibit Notch1 activation in SKOV3 cells for the gene therapy of ovarian cancer. The cationic cholesterol derivative, N -(cholesterylhemisuccinoyl-amino-3-propyl)- N , N -dimethylamine (DMAPA-chems) liposome, was incubated with siRNA at different nitrogen-to-phosphate ratios to form stabilized, near-spherical siRNA/DMAPA-chems nanoparticles with sizes of 100–200 nm and zeta potentials of 40–50 mV. The siRNA/DMAPA-chems nanoparticles protected siRNA from nuclease degradation in 25% fetal bovine serum. The nanoparticles exhibited high cell uptake and Notch1 gene knockdown efficiency in SKOV3 cells at an nitrogen-to-phosphate ratio of 100 and an siRNA concentration of 50 nM. They also inhibited the growth and promoted the apoptosis of SKOV3 cells. These results may provide the potential for using cationic cholesterol derivatives as efficient nonviral siRNA carriers for the suppression of Notch1 activation in ovarian cancer cells.

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Fighting against kidney diseases with small interfering RNA: opportunities and challenges

Cited by 25 publications

References 81 publications

An Overview of Various Carriers for siRNA Delivery

An Overview of Various Carriers for siRNA Delivery

Lipid-based Nanocarriers for siRNA Delivery: Challenges, Strategies and the Lessons Learned from the DODAX: MO Liposomal System

Efficient delivery of Notch1 siRNA to SKOV3 cells by cationic cholesterol derivative-based liposome

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