Effective lung-targeted RNAi in mice with peptide-based delivery of nucleic acid

Kurrikoff, Kaido; Freimann, Krista; Veiman, Kadi-Liis; Peets, Elin Madli; Piirsoo, Andres; Langel, Ülo

doi:10.1038/s41598-019-56455-2

Cited by 22 publications

(18 citation statements)

References 16 publications

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“…Peptide-based gene delivery systems have many advantages over other non-viral ones, including biocompatibility, biodegradability, limited toxicity and large-scale production capabilities [ 21 , 22 ]. Arginine-rich peptides belonging to cationic cell penetrating peptides (CPPs) are effective for in vitro and in vivo gene delivery [ 23 , 24 , 25 ]. Previous studies have shown that CPPs crosslinked by disulfide bonds promote efficient gene transfection and low cytotoxicity, due to the fact that disulfide bonds can be split by intracellular reducing compounds as glutathione for to release DNA [ 26 , 27 , 28 ].…”

Section: Introductionmentioning

confidence: 99%

Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma

et al. 2021

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Uterine leiomyoma (UL) is one of the most common benign tumors in women that often leads to many reproductive complications. Suicide genetherapy was suggested as a promising approach for UL treatment. In the present study, we describe iRGD ligand-conjugated cysteine-rich peptide carrier RGD1-R6 for targeted DNA delivery to αvβ3 integrin-expressing primary UL cells. The physico-chemical properties, cytotoxicity, transfection efficiency and specificity of DNA/RGD1-R6 polyplexes were investigated. TheHSV-1thymidine kinase encoding plasmid delivery to PANC-1pancreatic carcinoma cells and primary UL cells resulted in significant suicide gene therapy effects. Subsequent ganciclovir treatment decreased cells proliferative activity, induced of apoptosis and promoted cells death.The obtained results allow us to concludethatthe developed RGD1-R6 carrier can be considered a promising candidate for suicide gene therapy of uterine leiomyoma.

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Section: Introductionmentioning

confidence: 99%

Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma

et al. 2021

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“…In some cases, it was also possible to target a specific organ, as reported first for the NF55:pDNA nanoparticles [43]. Based on this result, Kurrikoff and colleagues performed in-depth analysis using PF14-and NF55-PBNs for the specific lung delivery of siRNA and pDNA using mice with acute lung inflammation and asthma [89]. Important anti-inflammatory effects were recorded in both disease models using siRNA targeting cytokine TNFα, resulting in decreased disease symptoms.…”

Section: Cell/organ Targetingmentioning

confidence: 89%

“…Based on this sequence, a novel amphipathic α-helical peptide, NF55, was designed for efficient in vivo DNA delivery by modifying the net charge and the helicity of the CPP [44,45]. More recently, Freimann and co-workers presented a new formulation approach called cryo-concentration for obtaining stable and homogeneous nanoparticles showing significantly higher bioactivity in vivo [89].…”

Section: Pepfect/nickfect Familymentioning

confidence: 99%

Peptide-Based Nanoparticles for Therapeutic Nucleic Acid Delivery

et al. 2021

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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.

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“…PF14 and NF55 preferentially transfect lung tissue upon their systemic administration with the complexed siRNA and pDNA encoding shRNA against cytokine TNFα in models of acute lung inflammation and asthma in mice, and showed efficient anti-inflammatory effects in both disease models [ 203 ].…”

Section: Targetingmentioning

confidence: 99%

Cell-Penetrating Peptides and Transportan

Langel

2021

Pharmaceutics

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In the most recent 25–30 years, multiple novel mechanisms and applications of cell-penetrating peptides (CPP) have been demonstrated, leading to novel drug delivery systems. In this review, I present a brief introduction to the CPP area with selected recent achievements. This is followed by a nostalgic journey into the research in my own laboratories, which lead to multiple CPPs, starting from transportan and paving a way to CPP-based therapeutic developments in the delivery of bio-functional materials, such as peptides, proteins, vaccines, oligonucleotides and small molecules, etc.

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Effective lung-targeted RNAi in mice with peptide-based delivery of nucleic acid

Cited by 22 publications

References 16 publications

Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma

Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma

Peptide-Based Nanoparticles for Therapeutic Nucleic Acid Delivery

Cell-Penetrating Peptides and Transportan

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