siRNA delivery for treatment of degenerative diseases, new hopes and challenges

Zahir‐Jouzdani, Forouhe; Mottaghitalab, Fatemeh; Dinarvand, Meshkat

doi:10.1016/j.jddst.2018.04.001

Cited by 26 publications

(11 citation statements)

References 189 publications

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“…RNA interference currently seems to be a growing technique in molecular biology due to its high potential in terms of therapeutic value [1]. In this sense, siRNA is the subject of clinical research, with encouraging results in the treatment of viral infections, neurodegenerative diseases, and cancer [2,3]. siRNA is formed by 2-stranded RNA molecules of approximately 20 nucleotides in length, whose strands complement each other perfectly.…”

Section: Introductionmentioning

confidence: 99%

Copper (II) Metallodendrimers Combined with Pro-Apoptotic siRNAs as a Promising Strategy Against Breast Cancer Cells

et al. 2020

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Cancer treatment with small interfering RNA (siRNA) is one of the most promising new strategies; however, transfection systems that increase its bioavailability and ensure its delivery to the target cell are necessary. Transfection systems may be just vehicular or could contain fragments with anticancer activity that achieves a synergistic effect with siRNA. Cationic carbosilane dendrimers have proved to be powerful tools as non-viral vectors for siRNA in cancer treatment, and their activity might be potentiated by the inclusion of metallic complexes in its dendritic structure. We have herein explored the interaction between Schiff-base carbosilane copper (II) metallodendrimers, and pro-apoptotic siRNAs. The nanocomplexes formed by metallodendrimers and different siRNA have been examined for their zeta potential and size, and by transmission electron microscopy, fluorescence polarisation, circular dichroism, and electrophoresis. The internalisation of dendriplexes has been estimated by flow cytometry and confocal microscopy in a human breast cancer cell line (MCF-7), following the ability of these metallodendrimers to deliver the siRNA into the cell. Finally, in vitro cell viability experiments have indicated effective interactions between Cu (II) dendrimers and pro-apoptotic siRNAs: Mcl-1 and Bcl-2 in breast cancer cells. Combination of the first-generation derivatives with chloride counterions and with siRNA increases the anticancer activity of the dendriplex constructs and makes them a promising non-viral vector.

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Section: Introductionmentioning

confidence: 99%

Copper (II) Metallodendrimers Combined with Pro-Apoptotic siRNAs as a Promising Strategy Against Breast Cancer Cells

et al. 2020

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“…The naked or unmodified siRNA is unstable in the systemic circulation and more susceptible to A-type nucleases, which are ubiquitous in intracellular and extracellular space [ 47 ]. Besides, fast renal clearance results in the very short half-life of siRNA, ranging from 5–10 min [ 48 , 49 , 50 ]. Nucleases in plasma or tissues degrade the unmodified siRNA in few minutes to 1 h, potentially limiting the use of siRNA-based therapeutics [ 51 , 52 ].…”

Section: Intravascular Degradation and Renal Clearancementioning

confidence: 99%

Overcoming Barriers for siRNA Therapeutics: From Bench to Bedside

et al. 2020

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The RNA interference (RNAi) pathway possesses immense potential in silencing any gene in human cells. Small interfering RNA (siRNA) can efficiently trigger RNAi silencing of specific genes. FDA Approval of siRNA therapeutics in recent years garnered a new hope in siRNA therapeutics. However, their therapeutic use is limited by several challenges. siRNAs, being negatively charged, are membrane-impermeable and highly unstable in the systemic circulation. In this review, we have comprehensively discussed the extracellular barriers, including enzymatic degradation of siRNAs by serum endonucleases and RNAases, rapid renal clearance, membrane impermeability, and activation of the immune system. Besides, we have thoroughly described the intracellular barriers such as endosomal trap and off-target effects of siRNAs. Moreover, we have reported most of the strategies and techniques in overcoming these barriers, followed by critical comments in translating these molecules from bench to bedside.

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“…Cerebrospinal fluid (CSF), obtained via lumbar puncture (LP), is a key component of research for Alzheimer’s disease and neurodegenerative disorders when it offers no diagnostic or therapeutic advantage. Indications for research LP will increase as both disease progression and response to putative therapeutics in research settings are monitored by analysis of CSF samples 1 2…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid sampling for research of Alzheimer’s disease and other neurodegenerative diseases when lumbar punctures are performed by anaesthetists

et al. 2022

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ObjectivesAn increasing number of people are undergoing lumbar puncture (LP) for the purposes of research. Performing LP for research purposes introduces considerations that differ from LP performed for clinical, diagnostic or therapeutic reasons. The demand for research LP will greatly increase as biomarkers are used to both diagnose and monitor disease progression in clinical trials. Minimising adverse events is paramount because research participants receive no clinical benefit and often need repeat procedures. We describe the experience of performing LP for research by anaesthetists.MethodsWe reviewed the clinical protocol and incidence of adverse events in 326 research LP in an anaesthesia department.ResultsThere was a lower incidence of adverse events compared with previous reports when LP was undertaken for clinical reasons. The incidence of severe post-LP headache was 1.3% when an atraumatic spinal needle with a 27 gauge tip and a 22 gauge shaft was used.ConclusionsWe describe the practice to sample cerebrospinal fluid (CSF) by LP for research purposes. Specific practices include the sitting position of the participant, aspiration rather than passive CSF withdrawal, attention to the sterility of the procedure, monitoring of vital signs and importantly the use of 22/27 gauge microtip spinal needle.Trial registration numbersACTRN12612000493842, NCT04623242.

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siRNA delivery for treatment of degenerative diseases, new hopes and challenges

Cited by 26 publications

References 189 publications

Copper (II) Metallodendrimers Combined with Pro-Apoptotic siRNAs as a Promising Strategy Against Breast Cancer Cells

Copper (II) Metallodendrimers Combined with Pro-Apoptotic siRNAs as a Promising Strategy Against Breast Cancer Cells

Overcoming Barriers for siRNA Therapeutics: From Bench to Bedside

Cerebrospinal fluid sampling for research of Alzheimer’s disease and other neurodegenerative diseases when lumbar punctures are performed by anaesthetists

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