Optimization of in vivo DNA delivery with NickFect peptide vectors

Freimann, Krista; Arukuusk, Piret; Kurrikoff, Kaido; Vasconcelos, Luis; Veiman, Kadi-Liis; Uusna, Julia; Margus, Helerin; García-Sosa, Alfonso T.; Pooga, Margus; Langel, Ülo

doi:10.1016/j.jconrel.2016.09.022

Cited by 63 publications

(74 citation statements)

References 31 publications

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“… 3 Recently, we have designed highly promising transfection reagent NF55 for transduction of nucleic acid molecules into cells. 4 NF55 forms stable particles with nucleic acids and is an effective in vivo transfection reagent, enabling induction of gene expression with efficiency that is comparable to the best transfection reagents available at the moment. 4 …”

Section: Introductionmentioning

confidence: 99%

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Formulation of Stable and Homogeneous Cell-Penetrating Peptide NF55 Nanoparticles for Efficient Gene Delivery In Vivo

Freimann

Arukuusk

Kurrikoff

et al. 2018

Molecular Therapy - Nucleic Acids

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Although advances in genomics and experimental gene therapy have opened new possibilities for treating otherwise incurable diseases, the transduction of nucleic acids into the cells and delivery in vivo remain challenging. The high molecular weight and anionic nature of nucleic acids require their packing into nanoparticles for the delivery. The efficacy of nanoparticle drugs necessitates the high bioactivity of constituents, but their distribution in organisms is mostly governed by the physical properties of nanoparticles, and therefore, generation of stable particles with strictly defined characteristics is highly essential. Using previously designed efficient cell-penetrating peptide NF55, we searched for strategies enabling control over the nanoparticle formation and properties to further improve transfection efficacy. The size of the NF55/pDNA nanoparticles correlates with the concentration of its constituents at the beginning of assembly, but characteristics of nanoparticles measured by DLS do not reliably predict the applicability of particles in in vivo studies. We introduce a new formulation approach called cryo-concentration, where we acquired stable and homogeneous nanoparticles for administration in vivo. The cryo-concentrated NF55/pDNA nanoparticles exhibit several advantages over standard formulation: They have long shelf-life and do not aggregate after reconstitution, have excellent stability against enzymatic degradation, and show significantly higher bioactivity in vivo.

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Section: Introductionmentioning

confidence: 99%

“… 4 NF55 forms stable particles with nucleic acids and is an effective in vivo transfection reagent, enabling induction of gene expression with efficiency that is comparable to the best transfection reagents available at the moment. 4 …”

Section: Introductionmentioning

confidence: 99%

Formulation of Stable and Homogeneous Cell-Penetrating Peptide NF55 Nanoparticles for Efficient Gene Delivery In Vivo

Freimann

Arukuusk

Kurrikoff

et al. 2018

Molecular Therapy - Nucleic Acids

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“…Addition of fatty acid increases delivery efficiency considerably,21, 31, 32, 33, 34 and amphipathy may have a considerable impact on CPP efficiency 35 . For example, PF3 was able to form complexes at MR15, while TP10 did not form stable complexes at tested MRs, although it was reported to form complexes at MR50 36 .…”

Section: Discussionmentioning

confidence: 98%

The Formation of Nanoparticles between Small Interfering RNA and Amphipathic Cell-Penetrating Peptides

Pärnaste

Arukuusk

Langel

et al. 2017

Molecular Therapy - Nucleic Acids

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Cell-penetrating peptides (CPPs) are delivery vectors widely used to aid the transport of biologically active cargoes to intracellular targets. These cargoes include small interfering RNAs (siRNA) that are not naturally internalized by cells. Elucidating the complexities behind the formation of CPP and cargo complexes is crucial for understanding the processes related to their delivery. In this study, we used modified analogs of the CPP transportan10 and investigated the binding properties of these CPPs to siRNA, the formation parameters of the CPP/siRNA complexes, and their stabiliy to enzymatic degradation. We conclude that the pH dependent change of the net charge of the CPP may very well be the key factor leading to the high delivery efficiency and the optimal binding strength between CPPs to siRNAs, while the hydrophobicity, secondary structure of the CPP, and the positions of the positive charges are responsible for the stability of the CPP/siRNA particles. Also, CPPs with distinct hydrophobic and hydrophilic regions may assemble into nanoparticles that could be described as core-shell formulations.

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“…With ornithine as a side chain instead of lysine, NickFect51 exhibited promising endosomolytic properties [ 67 ] and greater transfection efficiency in nucleic acid delivery [ 68 ]. By altering the net charges and helicity, amphipathic α-helical peptide NickFect55 delivered pDNA into tumors in mice bearing intracranial glioblastoma or subcutaneous Neuro2a/HT1080 tumors [ 69 ].…”

Section: Sequence-defined Macromolecular Carriersmentioning

confidence: 99%

Non-Viral Targeted Nucleic Acid Delivery: Apply Sequences for Optimization

Wang

Wagner

2020

Pharmaceutics

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In nature, genomes have been optimized by the evolution of their nucleic acid sequences. The design of peptide-like carriers as synthetic sequences provides a strategy for optimizing multifunctional targeted nucleic acid delivery in an iterative process. The optimization of sequence-defined nanocarriers differs for different nucleic acid cargos as well as their specific applications. Supramolecular self-assembly enriched the development of a virus-inspired non-viral nucleic acid delivery system. Incorporation of DNA barcodes presents a complementary approach of applying sequences for nanocarrier optimization. This strategy may greatly help to identify nucleic acid carriers that can overcome pharmacological barriers and facilitate targeted delivery in vivo. Barcode sequences enable simultaneous evaluation of multiple nucleic acid nanocarriers in a single test organism for in vivo biodistribution as well as in vivo bioactivity.

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Optimization of in vivo DNA delivery with NickFect peptide vectors

Cited by 63 publications

References 31 publications

Formulation of Stable and Homogeneous Cell-Penetrating Peptide NF55 Nanoparticles for Efficient Gene Delivery In Vivo

Formulation of Stable and Homogeneous Cell-Penetrating Peptide NF55 Nanoparticles for Efficient Gene Delivery In Vivo

The Formation of Nanoparticles between Small Interfering RNA and Amphipathic Cell-Penetrating Peptides

Non-Viral Targeted Nucleic Acid Delivery: Apply Sequences for Optimization

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