Supramolecular assemblies in functional siRNA delivery: Where do we stand?

Aliabadi, Hamidreza M.; Landry, Breanne; Sun, Chongbo; Tang, Tian; Uludağ, Hasan

doi:10.1016/j.biomaterials.2011.11.079

Cited by 123 publications

(99 citation statements)

References 263 publications

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“…Screening the efficiency of the recombinant protein siRNA delivery GAPDH siRNA on HeLa cell GAPDH. (Haupenthal et al, 2006), short serum half-life (Dykxhoorn et al, 2006;Raemdonck et al, 2008), negligible cellular internalization (Aliabadi et al, 2012), etc. The CPP, an efficient carrier for diverse cargos, could deliver siRNA via covalent conjugated or noncovalent charge interaction; however, the negatively charged siRNA can abolish the cell penetrating ability of CPP (Lee et al, 2013) via charge neutralizing.…”

Section: Discussionmentioning

confidence: 99%

Six-cell penetrating peptide-based fusion proteins for siRNA delivery

Tsui

2014

Drug Delivery

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The siRNA deliveries, for the siRNA's high negative charge, short serum half life, poor cellular internalization, etc, are still the key barriers for its application in clinic. In this study, several cell penetrating peptide (CPP) and dsRNA binding domain (dsRBD)-based fusion proteins have been developed and screened as the siRNA vector. The siRNA binding ability was measured by the agarose gel retardation, the cell uptaking was characterized under fluorescence microscopy, and further more RNAi effect was evaluated on the endogenous (GAPDH, western blot) and exogenous (GFP, flow cytometry analysis) genes in HeLa cell. Finally, the cytotoxicity was assessed on HeLa cells using cell counting kit-8. The efficiency of siRNA delivery by the CPP-dsRBD fusion protein was the CPP and the dsRBD dependent. Three fusion proteins showed similar efficiency of siRNA delivery when comparing to Lipofectamine RNAi Max as the siRNA carrier. These results indicated that these CPP-dsRBD-based fusion proteins were promising candidates as siRNA carriers.

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Section: Discussionmentioning

confidence: 99%

Six-cell penetrating peptide-based fusion proteins for siRNA delivery

Tsui

2014

Drug Delivery

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“…With siRNA, effective carriers have been intensely explored in the cancer therapeutics field. (126) It is likely that some of the effective carriers used for anticancer therapy will be effective in delivering siRNA to stimulate bone repair. Delivering miRNAs or oligonucleotides capable of modulating intracellular microRNAs is at infancy, with no animal studies reported to date.…”

Section: Perspectivementioning

confidence: 99%

Realizing the potential of gene-based molecular therapies in bone repair

Rose

Uludağ

2013

Journal of Bone and Mineral Research

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A better understanding of osteogenesis at genetic and biochemical levels is yielding new molecular entities that can modulate bone regeneration and potentially act as novel therapies in a clinical setting. These new entities are motivating alternative approaches for bone repair by utilizing DNA-derived expression systems, as well as RNA-based regulatory molecules controlling the fate of cells involved in osteogenesis. These sophisticated mediators of osteogenesis, however, pose unique delivery challenges that are not obvious in deployment of conventional therapeutic agents. Viral and nonviral delivery systems are actively pursued in preclinical animal models to realize the potential of the gene-based medicines. This article will summarize promising bone-inducing molecular agents on the horizon as well as provide a critical review of delivery systems employed for their administration. Special attention was paid to synthetic (nonviral) delivery systems because they are more likely to be adopted for clinical testing because of safety considerations. We present a comparative analysis of dose-response relationships, as well as pharmacokinetic and pharmacodynamic features of various approaches, with the purpose of clearly defining the current frontier in the field. We conclude with the authors' perspective on the future of genebased therapy of bone defects, articulating promising research avenues to advance the field of clinical bone repair. © 2013 American Society for Bone and Mineral Research. KEY WORDS: OSTEOGENESIS; BIOENGINEERING; MOLECULAR PATHWAYS; GENE-BASED THERAPYClinical Need for New Bone-Regeneration Strategies N early 2.2 million bone grafts are performed worldwide annually (1) and up to 20% of fractures are hampered by impaired healing. (2) The economic impact of nonunions is enormous, with the cost of spinal fusions alone reaching $20 billion annually. (3) The gold standard for repair of large segmental defects remains autologous grafts, where bone harvested from a non-weight-bearing site, usually the iliac crest, is used to repair defects. Bone grafts, however, are limited in several aspects, including potency of the grafts and the physiological detriment resulting from harvest surgery. Allografts are alternatively employed, where donor tissue is used to repair the defect, but the risk of disease transmission is always a concern. Allografts are extensively processed to reduce this risk, but osteopotency of the graft could be decreased in this way. (4) Demineralized bone matrix derived from decalcified bone can similarly act as a substitute; its potency, however, is variable and depends on the processing conditions. Synthetic scaffolds have been used to provide a hospitable environment for new bone formation. Scaffolds have been constructed from the organic (collagen) and inorganic (hydroxyapatite [HA]) components of bone, but such scaffolds are incapable of inducing osteogenesis on their own and they are more suitable for smaller defects.Osteogenic proteins are frequently employed to render ost...

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“…Many efforts for the improvement of nonviral vectors are focused on cationic polymers that interact with negatively charged DNA or RNAi. Polymers, including poly(l-lysine)-palmitic acid, poly(l-lysine) and polyethylenimine, condense the genetic material into particles of 200-300 nm in diameter, protect them from enzymes and facilitate cellular entrance [94,97]. These complexes of polymers and genetic material (called 'polyplexes') have a transfection efficiency that is equivalent to adenoviral vectors [97].…”

Section: A U T H O R P R O O Fmentioning

confidence: 99%

“…The cytotoxicity of 'polyplexes', nanoparticles and nanotubes has been evaluated in stem cells and the results showed that, in general, the toxicity correlates with the chemistry, concentration, size, shape and coating of the nanomaterials [97,98].…”

Section: A U T H O R P R O O Fmentioning

confidence: 99%

Nanodentistry: Combining Nanostructured Materials and Stem Cells for Dental Tissue Regeneration

2012

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Regenerative dentistry represents an attractive multidisciplinary therapeutic approach that complements traditional restorative/surgery techniques and benefits from recent advances in stem cell biology, molecular biology, genomics and proteomics. Materials science is important in such advances to move regenerative dentistry from the laboratory to the clinic. The design of novel nanostructured materials, such as biomimetic matrices and scaffolds for controlling cell fate and differentiation, and nanoparticles for diagnostics, imaging and targeted treatment, is needed. The combination of nanotechnology, which allows the creation of sophisticated materials with exquisite fine structural detail, and stem cell biology turns out to be increasingly useful in regenerative medicine. The administration to patients of dynamic biological agents comprising stem cells, bioactive scaffolds and/or nanoparticles will certainly increase the regenerative impact of dental pathological tissues. This overview briefly describes some of the actual benefits and future possibilities of nanomaterials in the emerging field of stem cell-based regenerative dentistry.

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Supramolecular assemblies in functional siRNA delivery: Where do we stand?

Cited by 123 publications

References 263 publications

Six-cell penetrating peptide-based fusion proteins for siRNA delivery

Six-cell penetrating peptide-based fusion proteins for siRNA delivery

Realizing the potential of gene-based molecular therapies in bone repair

Nanodentistry: Combining Nanostructured Materials and Stem Cells for Dental Tissue Regeneration

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