siRNA: Mechanism of action, challenges, and therapeutic approaches

Alshaer, Walhan; Zureigat, Hadil; Karaki, Arwa Al; Al-Kadash, Abdulfattah; Gharaibeh, Lobna; Hatmal, Ma’mon M.; Aljabali, Alaa A. A.; Awidi, Abdalla

doi:10.1016/j.ejphar.2021.174178

Cited by 224 publications

(136 citation statements)

References 99 publications

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“…In this study, the group opted to deliver small interfering RNAs (siRNA) to HeLa cells. siRNAs are short (∼22 nt) duplex strands of RNA comprised of a sense/passenger strand and an antisense/guide strand ( Table 2 ) ( Alshaer et al, 2021 ). siRNA can be used for therapeutic purposes of many diseases due to its ability to regulate gene expression by interfering with the normal replication process of RNA ( Bramsen and Kjems, 2012 ; Fakhr et al, 2016 ).…”

Section: Ddss With Switches—controlled By Phmentioning

confidence: 99%

Molecular Switches—Tools for Imparting Control in Drug Delivery Systems

2022

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Cancer is a globally prevalent cause of premature mortality. Of growing interest is the development of novel anticancer therapies and the optimisation of associated risks. Major issues presently facing conventional anticancer therapies include systemic toxicity, poor solubility, membrane permeability, and multidrug resistance Nanocarriers have been employed to address these issues. Nanocarriers encapsulate anticancer drugs, enabling them to bypass biological barriers and minimise their adverse side effects. These drug delivery systems offer extensive benefits as they can be modified to gravitate towards specific environmental conditions. To further enhance the safety and efficacy of these drug carriers, modern developments have included incorporating a molecular switching mechanism into their structure. These molecular switches are responsive to endogenous and exogenous stimuli and may undergo reversible and repeatable conformational changes when activated. The incorporation of molecular switches can, therefore, impart stimuli-responsive drug-release control on a DDS. These stimuli can then be manipulated to offer precise dosage control over the drug release at a specific target site. This review discusses recent developments in the design of DDSs incorporating light and pH-responsive molecular switches as drug release controllers.

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Section: Ddss With Switches—controlled By Phmentioning

confidence: 99%

Molecular Switches—Tools for Imparting Control in Drug Delivery Systems

2022

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“…This way, stability and translation are regulated and inhibited [37]. A clear disadvantage is that these approaches require a carrier for their protection and efficient delivery into the target cells [38]. The activity of small interfering RNAs (siRNA) in RNA interference (a biological process in which RNA molecules inhibit gene expression) is dependent on its binding ability to the RNA-induced silencing complex (RISC).…”

Section: Transcription Factor Decoy Technologymentioning

confidence: 99%

Section: Transcription Factor Decoy Technologymentioning

confidence: 99%

“…In a murine heterotopic aortic transplant model (mgR/mgR mice), the adenovirus-induced overexpression of TIMP-1 led to massive intima hyperplasia in the Marfan aorta [ 18 ]. However, TIMP-1 overexpression significantly reduced MMP9-activity in a heterotopic aortic transplant model when delivered by apathogenic AAVs [ 38 ]. As AAV transduction did not result in intima hyperplasia in Marfan aortic grafts [ 14 ], it represents a possible beneficial alternative gene therapy approach to adenovirus.…”

Section: Concepts Of Others and Outlookmentioning

confidence: 99%

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Translational Medicine: Towards Gene Therapy of Marfan Syndrome

Kallenbach

Remes

Müller

et al. 2022

JCM

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Marfan syndrome (MFS) is one of the most common inherited disorders of connective tissue caused by mutations of the fibrillin-1 gene (FBN1). Vascular abnormalities, such as the enlargement of the aorta with the risk of life-threatening rupture are frequently observed. However, current treatment is limited and therapeutic options focus solely on symptomatic therapy. Gene therapy focuses on genetically modifying cells to produce a therapeutic effect and may be a promising treatment option for MFS. Here, we first provide an overview of the historical background and characterization of MFS. Subsequently, we summarise current gene therapy options and possible translational concepts for this inherited disorder that affects connective tissue.

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“…Nucleic acid medicines including small interfering RNAs (siRNAs), antisense oligonucleotides, and RNA aptamers have been developed as new therapeutic agents that directly suppress target molecules and control the pathophysiology of many diseases [1][2][3][4]. Although this approach is effective against age-related macular degeneration and muscular dystrophy when these agents are administered locally [2,5], targeted delivery of siRNAs into cancer cells, particularly hematologic cancer cells, via systemic administration is limited by a lack of efficient and cell-specific delivery systems.…”

Section: Introductionmentioning

confidence: 99%

Successful Incorporation of Exosome-Capturing Antibody-siRNA Complexes into Multiple Myeloma Cells and Suppression of Targeted mRNA Transcripts

Soma

Yamayoshi

Toda

et al. 2022

Cancers

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Nucleic acid medicines have been developed as new therapeutic agents against various diseases; however, targeted delivery of these reagents into cancer cells, particularly hematologic cancer cells, via systemic administration is limited by the lack of efficient and cell-specific delivery systems. We previously demonstrated that monoclonal antibody (mAb)-oligonucleotide complexes targeting exosomal microRNAs with linear oligo-D-arginine (Arg) linkers were transferred into solid cancer cells and inhibited exosomal miRNA functions. In this study, we developed exosome-capturing anti-CD63 mAb-conjugated small interfering RNAs (siRNAs) with branched Arg linkers and investigated their effects on multiple myeloma (MM) cells. Anti-CD63 mAb-conjugated siRNAs were successfully incorporated into MM cells. The incorporation of exosomes was inhibited by endocytosis inhibitors. We also conducted a functional analysis of anti-CD63 mAb-conjugated siRNAs. Ab-conjugated luciferase+ (luc+) siRNAs significantly decreased the luminescence intensity in OPM-2-luc+ cells. Moreover, treatment with anti-CD63 mAb-conjugated with MYC and CTNNB1 siRNAs decreased the mRNA transcript levels of MYC and CTNNB1 to 52.5% and 55.3%, respectively, in OPM-2 cells. In conclusion, exosome-capturing Ab-conjugated siRNAs with branched Arg linkers can be effectively delivered into MM cells via uptake of exosomes by parental cells. This technology has the potential to lead to a breakthrough in drug delivery systems for hematologic cancers.

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siRNA: Mechanism of action, challenges, and therapeutic approaches

Cited by 224 publications

References 99 publications

Molecular Switches—Tools for Imparting Control in Drug Delivery Systems

Molecular Switches—Tools for Imparting Control in Drug Delivery Systems

Translational Medicine: Towards Gene Therapy of Marfan Syndrome

Successful Incorporation of Exosome-Capturing Antibody-siRNA Complexes into Multiple Myeloma Cells and Suppression of Targeted mRNA Transcripts

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