Oxime Ether Lipids Containing Hydroxylated Head Groups are More Superior siRNA Delivery Agents than their Nonhydroxylated Counterparts

Gupta, K. C.; Mattingly, Stephanie J.; Knipp, Ralph J.; Afonin, Kirill A.; Viard, Mathias; Bergman, Joseph T; Stepler, Marissa; Nantz, Michael H.; Puri, Anu; Shapiro, Bruce A.

doi:10.2217/nnm.15.105

Cited by 19 publications

(12 citation statements)

References 47 publications

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“…Investigating different potential carriers, such as lipids or cell-penetrating peptides, for in vivo delivery of RNA therapeutics is therefore one area of RNA nanotechnology that would benefit from SAS-based approaches. Experiments with NANPs employing various carriers such as magnetic nanoparticles [81], lipids [82], mesoporous silica-based nanoparticles [79], polysilsesquioxane [83], and bolaamphiphiles or ‘bolas’ [84,85] have already been successfully initiated. The use of SANS can significantly improve our current understanding of the interactions between the NANPs and carriers, which can further improve NANP delivery in vivo.…”

Section: Discussionmentioning

confidence: 99%

Small-Angle Scattering as a Structural Probe for Nucleic Acid Nanoparticles (NANPs) in a Dynamic Solution Environment

et al. 2019

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Nucleic acid-based technologies are an emerging research focus area for pharmacological and biological studies because they are biocompatible and can be designed to produce a variety of scaffolds at the nanometer scale. The use of nucleic acids (ribonucleic acid (RNA) and/or deoxyribonucleic acid (DNA)) as building materials in programming the assemblies and their further functionalization has recently established a new exciting field of RNA and DNA nanotechnology, which have both already produced a variety of different functional nanostructures and nanodevices. It is evident that the resultant architectures require detailed structural and functional characterization and that a variety of technical approaches must be employed to promote the development of the emerging fields. Small-angle X-ray and neutron scattering (SAS) are structural characterization techniques that are well placed to determine the conformation of nucleic acid nanoparticles (NANPs) under varying solution conditions, thus allowing for the optimization of their design. SAS experiments provide information on the overall shapes and particle dimensions of macromolecules and are ideal for following conformational changes of the molecular ensemble as it behaves in solution. In addition, the inherent differences in the neutron scattering of nucleic acids, lipids, and proteins, as well as the different neutron scattering properties of the isotopes of hydrogen, combined with the ability to uniformly label biological macromolecules with deuterium, allow one to characterize the conformations and relative dispositions of the individual components within an assembly of biomolecules. This article will review the application of SAS methods and provide a summary of their successful utilization in the emerging field of NANP technology to date, as well as share our vision on its use in complementing a broad suite of structural characterization tools with some simulated results that have never been shared before.

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Section: Discussionmentioning

confidence: 99%

Small-Angle Scattering as a Structural Probe for Nucleic Acid Nanoparticles (NANPs) in a Dynamic Solution Environment

et al. 2019

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“…groups are better transfecting and silencing agents than the saturated and non-hydroxylated lipids [62]. Further detailed studies will validate the application of OELs in broader prospects for RNAi therapy.…”

Section: Oxime Ether Lipidsmentioning

confidence: 88%

“…Oxime ether lipids (OELs) are a relatively new class of cationic agents explored as efficient transfection tools [ 61 , 62 ]. In contrast to commonly used transfection lipids, OELs contain oxime ether bonds ( Figure 2C ) and can be synthesized by simple and efficient click chemistry [ 63 ].…”

Section: Overview Of Nvcvsmentioning

confidence: 99%

“…By synthesizing a variety of oxime ether lipids we demonstrated that hydrophobicity and the degree of unsaturation of the fatty acyl chains play a role in siRNA activity. Moreover, the head group polarities perform a role in the electrostatic interaction with siRNAs, protection from nucleases, uptake, and gene silencing in a cell culture system [ 62 ]. The structures of symmetric OELs, containing either saturated or unsaturated hydrophobic fatty acyl chains are shown in Figure 2C .…”

Section: Overview Of Nvcvsmentioning

confidence: 99%

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Functionalized non-viral cationic vectors for effective siRNA induced cancer therapy

Gupta

Puri

Shapiro

2017

DNA and RNA Nanotechnology

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RNA interference (RNAi) has been regarded as a vital asset in the field of therapeutics as it has the capability to silence various disease causing genes including those that cause cancer. Small non-coding RNA molecules such as short interfering RNAs (siRNAs) are one of the extensively studied RNAi inducers for gene modulations. However, the delivery of RNAi inducers including siRNAs is compromised due to the barriers imposed by the biological system such as degradation by nucleases, rapid clearance, high anionic charge, immunogenicity and off-target effects. Viral vectors, in general exhibit high transfection efficiencies but are expensive and likely to confer immunological and safety issues. Therefore, non-viral cationic vectors (NVCVs) have received considerable attention to not only address these issues but also for developing efficacious siRNA delivery vectors. In this review, we will first discuss the historical development of various NVCVs and then will discuss functionalized NVCVs with linkers that provide stability, as well as respond to the cancer cell environment and with cancer cell receptor specific ligands to explicitly target them for improved siRNA efficacy. Multifunctional NVCVs (MNVCVs) that employ multiple synergistically working components to aid siRNA delivery efficacy are also discussed.

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“…NANPs’ ability to successfully combat diseases at their source has already been confirmed by multiple animal studies [25,38,39,40,41,42,43]. Additionally, the design principles being developed in RNA nanotechnology address fundamental problems relevant to the biophysics of RNA co-transcriptional folding [24,44,45,46,47], structure–activity relationships [48], and their physicochemical interactions with other classes of biomolecules (e.g., lipids [41,49,50], proteins [51,52]) or inorganic materials [53,54].…”

Section: Introductionmentioning

confidence: 98%

Smart-Responsive Nucleic Acid Nanoparticles (NANPs) with the Potential to Modulate Immune Behavior

Chandler

Afonin

2019

Nanomaterials

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Nucleic acids are programmable and biocompatible polymers that have beneficial uses in nanotechnology with broad applications in biosensing and therapeutics. In some cases, however, the development of the latter has been impeded by the unknown immunostimulatory properties of nucleic acid-based materials, as well as a lack of functional dynamicity due to stagnant structural design. Recent research advancements have explored these obstacles in tandem via the assembly of three-dimensional, planar, and fibrous cognate nucleic acid-based nanoparticles, called NANPs, for the conditional activation of embedded and otherwise quiescent functions. Furthermore, a library of the most representative NANPs was extensively analyzed in human peripheral blood mononuclear cells (PBMCs), and the links between the programmable architectural and physicochemical parameters of NANPs and their immunomodulatory properties have been established. This overview will cover the recent development of design principles that allow for fine-tuning of both the physicochemical and immunostimulatory properties of dynamic NANPs and discuss the potential impacts of these novel strategies.

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Oxime Ether Lipids Containing Hydroxylated Head Groups are More Superior siRNA Delivery Agents than their Nonhydroxylated Counterparts

Cited by 19 publications

References 47 publications

Small-Angle Scattering as a Structural Probe for Nucleic Acid Nanoparticles (NANPs) in a Dynamic Solution Environment

Small-Angle Scattering as a Structural Probe for Nucleic Acid Nanoparticles (NANPs) in a Dynamic Solution Environment

Functionalized non-viral cationic vectors for effective siRNA induced cancer therapy

Smart-Responsive Nucleic Acid Nanoparticles (NANPs) with the Potential to Modulate Immune Behavior

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