Modular cell-internalizing aptamer nanostructure enables targeted delivery of large functional RNAs in cancer cell lines

Porciani, David; Cardwell, Leah N.; Tawiah, Kwaku D; Alam, Khalid K.; Lange, Margaret J.; Daniëls, Mark A.; Burke, Donald H.

doi:10.1038/s41467-018-04691-x

Cited by 51 publications

(52 citation statements)

References 70 publications

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“…Similarly, aptamers were used to provide large RNA payloads (175–250 nt) to several human B cell cancer lines. Aptamers conjugated with fluorogenic RNA reporter specifically bound with leukemic B cell lines, thus caused fluorescence that lasted for ≥2 h [ 55 ], showing the potential use of the system for drug delivery to cancer cells. In another study, LC09 aptamer was used to specifically target the vascular endothelial growth factor A (VEGFA) of osteosarcoma cancer cells, by functionalizing LC09 aptamer with a PEG-PEI-Cholesterol (PPC) lipopolymer that encapsulated Cas9 and CRISPR/Cas9 plasmids coding for VEGFA gRNA.…”

Section: Aptamers In Cancer Diagnosismentioning

confidence: 99%

Current Perspectives on Aptamers as Diagnostic Tools and Therapeutic Agents

2020

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Aptamers are synthetic single-stranded DNA or RNA sequences selected from combinatorial oligonucleotide libraries through the well-known in vitro selection and iteration process, SELEX. The last three decades have witnessed a sudden boom in aptamer research, owing to their unique characteristics, like high specificity and binding affinity, low immunogenicity and toxicity, and ease in synthesis with negligible batch-to-batch variation. Aptamers can specifically bind to the targets ranging from small molecules to complex structures, making them suitable for a myriad of diagnostic and therapeutic applications. In analytical scenarios, aptamers are used as molecular probes instead of antibodies. They have the potential in the detection of biomarkers, microorganisms, viral agents, environmental pollutants, or pathogens. For therapeutic purposes, aptamers can be further engineered with chemical stabilization and modification techniques, thus expanding their serum half-life and shelf life. A vast number of antagonistic aptamers or aptamer-based conjugates have been discovered so far through the in vitro selection procedure. However, the aptamers face several challenges for its successful clinical translation, and only particular aptamers have reached the marketplace so far. Aptamer research is still in a growing stage, and a deeper understanding of nucleic acid chemistry, target interaction, tissue distribution, and pharmacokinetics is required. In this review, we discussed aptamers in the current diagnostics and theranostics applications, while addressing the challenges associated with them. The report also sheds light on the implementation of aptamer conjugates for diagnostic purposes and, finally, the therapeutic aptamers under clinical investigation, challenges therein, and their future directions.

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Section: Aptamers In Cancer Diagnosismentioning

confidence: 99%

Current Perspectives on Aptamers as Diagnostic Tools and Therapeutic Agents

2020

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“…The aptamer‐tethered oligoguanine nucleotides self‐assembled to form Y‐shaped DNA structures, which were shown to have strong potential for cells specific drug delivery and improved therapeutic effects. Porciani et al engineered a cell‐internalizing aptamer nanostructure that enables targeted delivery of large functional RNAs in cancer cell lines. This platform exploited cell‐internalizing aptamers to accomplish cell‐type‐specific delivery, along with the fluorescence properties of RNA mimics of GFP as surrogates for other large RNA‐based payloads.…”

Section: Molecular Engineering Of Aptamer‐based Nanomaterials Toward mentioning

confidence: 99%

Molecular Engineering of Functional Nucleic Acid Nanomaterials toward In Vivo Applications

Zhang

Lan

2019

Adv Healthcare Materials

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equally exciting and perhaps more challenging field of application is toward their in vivo applications, including living animals and human bodies, in diverse areas, [2] such as sensing, drug delivery, medical imaging, and cancer therapy. However, most of these nanomaterials lack selectivity toward targets of interests. Therefore, to employ these nanomaterials for a wider range of in vivo applications, various molecular engineering approaches have been employed to obtained nanomaterials functionalized with biomolecules to enable selective targeting. [3][4][5] Among these biomolecules, functional nucleic acids, or FNAs, have shown the most promise.FNAs are DNA or RNA molecules that can interact with or bind to a specific analyte, resulting in a conformational change and/or a catalytic reaction. [6] As their names suggested, ribozymes and deoxyribozymes (called DNAzyme hereafter) can act as enzymes in the presence of cofactors to catalyze various reactions, including cleavage and ligation of RNA/DNA, and phosphorylation and peroxidation of DNA. On the other hand, riboswitches and DNA aptamers are antibody-like receptors that can bind target molecules with high affinity and selectivity. Furthermore, the binding abilities of riboswitches and aptamers can be combined with the enzymatic function of ribozymes or DNAzymes to form aptazymes so that the binding of targets can inhibit or enhance the catalytic activities. These nucleic acids, including DNAzymes, aptamers, and aptazymes, are collectively known as FNAs to emphasize their functions beyond the traditional genetic storage and transformations roles for DNA and RNA. Unlike DNA and RNA inside biological systems, FNAs are isolated via a combinatorial technique known as in vitro selection, or a process also known as systematic evolution of ligands by exponential enrichment (SELEX). The discovery of new functions of nucleic acids has not only resulted in major advances in the fields of molecular biology and biochemistry, but also revolutionized sensors designs for both in vitro and in vivo applications. [7,8] Over the past decade, numerous FNA-based nanomaterials have been developed. [9][10][11][12] Among these FNA-based nanosystems, the functions of FNAs can be categorized into two types: diagnostic function and therapeutic function. For the diagnostic function, the FNAs serve either as the biorecognition ligands for direct sensing and imaging of the Recent advances in nanotechnology and engineering have generated many nanomaterials with unique physical and chemical properties. Over the past decade, numerous nanomaterials are introduced into many research areas, such as sensors for environmental monitoring, food safety, point-ofcare diagnostics, and as transducers for solar energy transfer. Meanwhile, functional nucleic acids (FNAs), including nucleic acid enzymes, aptamers, and aptazymes, have attracted major attention from the biomedical community due to their unique target recognition and catalytic properties. Benefiting from the recent progress of molecular engine...

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“…The size of the delivered RNA might provide additional troubleshooting at the time of targeting but, as recently demonstrated by Porciani et al, the RNA payload does not affect the aptamer-based targeted delivery of such molecules [87]. They used Waz and C10.36 aptamers to specifically in vitro deliver both short and large RNAs to canine CLL17 B-cell lymphoma cells and canine CLGL-90 leukemia T cells.…”

Section: Interfering Rnasmentioning

confidence: 99%

Aptamer-iRNAs as Therapeutics for Cancer Treatment

et al. 2018

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Aptamers are single-stranded oligonucleotides (ssDNA or ssRNA) that bind and recognize their targets with high affinity and specificity due to their complex tertiary structure. Aptamers are selected by a method called SELEX (Systematic Evolution of Ligands by EXponential enrichment). This method has allowed the selection of aptamers to different types of molecules. Since then, many aptamers have been described for the potential treatment of several diseases including cancer. It has been described over the last few years that aptamers represent a very useful tool as therapeutics, especially for cancer therapy. Aptamers, thanks to their intrinsic oligonucleotide nature, present inherent advantages over other molecules, such as cell-based products. Owing to their higher tissue penetrability, safer profile, and targeting capacity, aptamers are likely to become a novel platform for the delivery of many different types of therapeutic cargos. Here we focus the review on interfering RNAs (iRNAs) as aptamer-based targeting delivered agents. We have gathered the most reliable information on aptamers as targeting and carrier agents for the specific delivery of siRNAs, shRNA, microRNAs, and antisense oligonucleotides (ASOs) published in the last few years in the context of cancer therapy.

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Modular cell-internalizing aptamer nanostructure enables targeted delivery of large functional RNAs in cancer cell lines

Cited by 51 publications

References 70 publications

Current Perspectives on Aptamers as Diagnostic Tools and Therapeutic Agents

Current Perspectives on Aptamers as Diagnostic Tools and Therapeutic Agents

Molecular Engineering of Functional Nucleic Acid Nanomaterials toward In Vivo Applications

Aptamer-iRNAs as Therapeutics for Cancer Treatment

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