scholarly journals Peptide-Based Nanoparticles for Therapeutic Nucleic Acid Delivery

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 583
Author(s):  
Prisca Boisguérin ◽  
Karidia Konate ◽  
Emilie Josse ◽  
Eric Vivès ◽  
Sébastien Deshayes
Keyword(s):  
Nucleic Acid ◽  
Delivery System ◽  
Viral Vectors ◽  
Positive Charge ◽  
Cell Penetrating Peptides ◽  
Nucleic Acid Delivery ◽  
Universal Approach ◽  
Biological Aspects

Gene therapy offers the possibility to skip, repair, or silence faulty genes or to stimulate the immune system to fight against disease by delivering therapeutic nucleic acids (NAs) to a patient. Compared to other drugs or protein treatments, NA-based therapies have the advantage of being a more universal approach to designing therapies because of the versatility of NA design. NAs (siRNA, pDNA, or mRNA) have great potential for therapeutic applications for an immense number of indications. However, the delivery of these exogenous NAs is still challenging and requires a specific delivery system. In this context, beside other non-viral vectors, cell-penetrating peptides (CPPs) gain more and more interest as delivery systems by forming a variety of nanocomplexes depending on the formulation conditions and the properties of the used CPPs/NAs. In this review, we attempt to cover the most important biophysical and biological aspects of non-viral peptide-based nanoparticles (PBNs) for therapeutic nucleic acid formulations as a delivery system. The most relevant peptides or peptide families forming PBNs in the presence of NAs described since 2015 will be presented. All these PBNs able to deliver NAs in vitro and in vivo have common features, which are characterized by defined formulation conditions in order to obtain PBNs from 60 nm to 150 nm with a homogeneous dispersity (PdI lower than 0.3) and a positive charge between +10 mV and +40 mV.

IMMU-53. STING-ING GLIOBLASTOMA WITH SPHERICAL NUCLEIC ACIDS

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi104-vi105
Author(s):  
Akanksha Mahajan ◽  
Lisa Hurley ◽  
Serena Tommasini-Ghelfi ◽  
Corey Dussold ◽  
Alexander Stegh ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
High Surface ◽  
Biological Properties ◽  
Innate Immune ◽  
Limiting Factors ◽  
Nucleic Acid Delivery ◽  
Sting Pathway ◽  
Spherical Nucleic Acids

Abstract The Stimulator of Interferon Genes (STING) pathway represents a major innate immune sensing mechanism for tumor-derived DNA. Modified cyclic dinucleotides (CDNs) that mimic the endogenous STING ligand cGAMP are currently being explored in patients with solid tumors that are amenable to intratumoral delivery. Inadequate bioavailability and insufficient lipophilicity are limiting factors for clinical CDN development, in particular when consideration is given to systemic administration approaches. We have shown that the formulation of oligonucleotides into Spherical Nucleic Acid (SNA) nanostructures, i.e.,the presentation of oligonucleotides at high density on the surface of nanoparticle cores, lead to biochemical and biological properties that are radically different from those of linear oligonucleotides. First-generation brain-penetrant siRNA-based SNAs (NCT03020017, recurrent GBM) have recently completed early clinical trials. Here, we report the development of a STING-agonistic immunotherapy by targeting cGAS, the sensor of cytosolic dsDNA upstream of STING, with SNAs presenting dsDNA at high surface density. The strategy of using SNAs exploits the ability of cGAS to raise STING responses by delivering dsDNA and inducing the catalytic production of endogenous CDNs. SNA nanostructures carrying a 45bp IFN-simulating dsDNA oligonucleotide, the most commonly used and widely characterized cGAS activator, potently activated the cGAS-STING pathway in vitro and in vivo. In a poorly immunogenic and highly aggressive syngeneic mouse glioma model, in which tumours were well-established, only one dose of intranasal treatment with STING-SNAs decelerated tumour growth, improved survival and importantly, was well-tolerated. Our use of SNAs addresses the challenges of nucleic acid delivery to intracranial tumor sites via intranasal route, exploits the binding of dsDNA molecules on the SNA surface to enhance the formation of a dimeric cGAS:DNA complex and establishes cGAS-agonistic SNAs as a novel class of immune-stimulatory modalities for triggering innate immune responses against tumor.

Cationic DOPC-Detergent Conjugates for Safe and Efficient in Vitro and in Vivo Nucleic Acid Delivery

ChemBioChem ◽  
2016 ◽  
Vol 17 (18) ◽  
pp. 1771-1783 ◽  
Author(s):  
Philippe Pierrat ◽  
Anne Casset ◽  
Pascal Didier ◽  
Dimitri Kereselidze ◽  
Marie Lux ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery

scholarly journals A Direct Comparison of in Vitro and in Vivo Nucleic Acid Delivery Mediated by Hundreds of Nanoparticles Reveals a Weak Correlation

Nano Letters ◽  
2018 ◽  
Vol 18 (3) ◽  
pp. 2148-2157 ◽  
Author(s):  
Kalina Paunovska ◽  
Cory D. Sago ◽  
Christopher M. Monaco ◽  
William H. Hudson ◽  
Marielena Gamboa Castro ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery ◽  
Weak Correlation

Components Simulation of Viral Envelope via Amino Acid Modified Chitosans for Efficient Nucleic Acid Delivery: In Vitro and In Vivo Study

2012 ◽  
Vol 23 (21) ◽  
pp. 2691-2699 ◽  
Author(s):  
Jing Chang ◽  
Xianghui Xu ◽  
Haiping Li ◽  
Yeting Jian ◽  
Gang Wang ◽  
...  
Keyword(s):  
Amino Acid ◽  
Nucleic Acid ◽  
Viral Envelope ◽  
In Vivo Study ◽  
Nucleic Acid Delivery

scholarly journals Tunable Composition of Dynamic Non-Viral Vectors over the DNA Polyplex Formation and Nucleic Acid Transfection

Polymers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1313 ◽  
Author(s):  
Lilia Clima ◽  
Bogdan Florin Craciun ◽  
Gabriela Gavril ◽  
Mariana Pinteala
Keyword(s):  
Molecular Weight ◽  
Nucleic Acid ◽  
Viral Vectors ◽  
Viral Vector ◽  
Transfection Efficiency ◽  
Binding Capacity ◽  
Nucleic Acid Delivery ◽  
Force Microscopy ◽  
Transmission Electron

Polyethylene glycol (PEG) functionalization of non-viral vectors represents a powerful tool through the formation of an overall surface charge shielding ability, which is fundamental for efficient nucleic acid delivery systems. The degree of non-viral vector PEGylation and the molecular weight of utilized PEG is crucial since the excessive use of PEG units may lead to a considerable reduction of the DNA-binding capacity and, subsequently, in a reduction of in vitro transfection efficiency. Herein, we report a detailed study on a series of dynamic combinatorial frameworks (DCFs) containing PEGylated squalene, poly-(ethyleneglycol)-bis(3-aminopropyl) of different lengths, and branched low molecular weight polyethylenimine components, reversibly connected in hyperbranched structures, as efficient dynamic non-viral vectors. The obtained frameworks were capable of forming distinct supramolecular amphiphilic architectures, shown by transmission electron microscopy (TEM) and dynamic light scattering (DLS), with sizes and stability depending on the length of PEG units. The interaction of PEGylated DCFs with nucleic acids was investigated by agarose gel retardation assay and atomic force microscopy (AFM), while their transfection efficiency (using pCS2+MT-Luc DNA as a reporter gene) and cytotoxicity were evaluated in HeLa cells. In addition, the data on the influence of the poly-(ethyleneglycol)-bis(3-aminopropyl) length in composition of designed frameworks over transfection efficiency and tolerance in human cells were analyzed and compared.

scholarly journals Internalisation and Biological Activity of Nucleic Acids Delivering Cell-Penetrating Peptide Nanoparticles Is Controlled by the Biomolecular Corona

2021 ◽  
Vol 14 (7) ◽  
pp. 667
Author(s):  
Annely Lorents ◽  
Maria Maloverjan ◽  
Kärt Padari ◽  
Margus Pooga
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Transfection Efficiency ◽  
Protein Corona ◽  
Blood Stream ◽  
Cell Penetrating Peptides ◽  
Biological Efficiency ◽  
Cell Penetrating

Nucleic acid molecules can be transferred into cells to alter gene expression and, thus, alleviate certain pathological conditions. Cell-penetrating peptides (CPPs) are vectors that can be used for transfecting nucleic acids as well as many other compounds. CPPs associate nucleic acids non-covalently, forming stable nanoparticles and providing efficient transfection of cells in vitro. However, in vivo, expected efficiency is achieved only in rare cases. One of the reasons for this discrepancy is the formation of protein corona around nanoparticles, once they are exposed to a biological environment, e.g., blood stream. In this study, we compared protein corona of CPP-nucleic acid nanoparticles formed in the presence of bovine, murine and human serum. We used Western blot and mass-spectrometry to identify the major constituents of protein corona forming around nanoparticles, showing that proteins involved in transport, haemostasis and complement system are its major components. We investigated physical features of nanoparticles and measured their biological efficiency in splice-correction assay. We showed that protein corona constituents might alter the fate of nanoparticles in vivo, e.g., by subjecting them to phagocytosis. We demonstrated that composition of protein corona of nanoparticles is species-specific that leads to dissimilar transfection efficiency and should be considered while developing delivery systems for nucleic acids.

scholarly journals Internalisation and biological activity of nucleic acids delivering cell-penetrating peptide nanoparticles is controlled by the biomolecular corona

2021 ◽  
Author(s):  
Annely Lorents ◽  
Maria Maloverjan ◽  
Kärt Padari ◽  
Margus Pooga
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Transfection Efficiency ◽  
Protein Corona ◽  
Blood Stream ◽  
Cell Penetrating Peptides ◽  
Biological Efficiency ◽  
Cell Penetrating

Nucleic acid molecules can be transferred into cells to alter gene expression and, thus, alleviate certain pathological conditions. Cell-penetrating peptides (CPPs) are vectors that can be used for transfecting nucleic acids as well as many other compounds. CPPs associate nucleic acids non-covalently, forming stable nanoparticles and providing efficient transfection of cells in vitro. However, in vivo, expected efficiency is achieved only in rare cases. One of the reasons for this discrepancy is formation of protein corona around nanoparticles, once they are exposed to a biological environment, e.g. blood stream. In this study, we compared CPP-nucleic acid nanoparticles formed in the presence of bovine, murine and human serum. We used Western blot and mass-spectrometry to identify the major constituents of protein corona forming around nanoparticles, showing that proteins involved in transport, haemostasis and complement system are its major components. We investigated physical features of nanoparticles, and measured their biological efficiency in splice-correction assay. We showed that protein corona constituents might alter the fate of nanoparticles in vivo, e.g. by subjecting them to phagocytosis. We demonstrated that composition of protein corona of nanoparticles is species-specific that leads to dissimilar transfection efficiency and should be taken into account while developing delivery systems for nucleic acids.

scholarly journals Enhancing the In Vitro and In Vivo Stabilities of Polymeric Nucleic Acid Delivery Nanosystems

2018 ◽  
Vol 30 (2) ◽  
pp. 325-337 ◽  
Author(s):  
Yuyuan Wang ◽  
Mingzhou Ye ◽  
Ruosen Xie ◽  
Shaoqin Gong
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acid Delivery

scholarly journals Sugar Functionalized Synergistic Dendrimers for Biocompatible Delivery of Nucleic Acid Therapeutics

Polymers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 1034 ◽  
Author(s):  
Shuqin Han ◽  
Tsogzolmaa Ganbold ◽  
Qingming Bao ◽  
Takashi Yoshida ◽  
Huricha Baigude
Keyword(s):  
Nucleic Acid ◽  
Sirna Delivery ◽  
Green Fluorescence Protein ◽  
Nucleic Acid Delivery ◽  
Cationic Polymers ◽  
Nucleic Acid Therapeutics ◽  
Fluorescence Protein ◽  
Interfering Rna

Sugars containing cationic polymers are potential carriers for in vitro and in vivo nucleic acid delivery. Monosaccharides such as glucose and galactose have been chemically conjugated to various materials of synergistic poly-lysine dendrimer systems for efficient and biocompatible delivery of short interfering RNA (siRNA). The synergistic dendrimers, which contain lipid conjugated glucose terminalized lysine dendrimers, have significantly lower adverse impact on cells while maintaining efficient cellular entry. Moreover, the synergistic dendrimers complexed to siRNA induced RNA interference (RNAi) in the cells and profoundly knocked down green fluorescence protein (GFP) as well as the endogenously expressing disease related gene Plk1. The new synergic dendrimers may be promising system for biocompatible and efficient siRNA delivery.

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