Efficient in vivo siRNA delivery by stabilized <scp>d</scp>-peptide-based lipid nanoparticles

Ganbold, Tsogzolmaa; Gerile, Gerile; Xiao, Hai; Baigude, Huricha

doi:10.1039/c6ra25862j

Cited by 12 publications

(14 citation statements)

References 30 publications

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“…Real-Time PCR: mRNA gene expression was determined using SYBR green quantitative real-time PCR (qt-PCR) on cDNA template. cDNA was generated from 1000 ng RNA per sample using oligo(dT) [12][13][14][15][16][17][18] primers and iScript cDNA Synthesis Kit (Biorad), according to manufacturer's instructions. Product was amplified with 20 × 10 −6 m forward and reverse primers of gene of interest and SybrGreen Mastermix (Life Technologies) on an Applied Biosystems 7900 real-time PCR.…”

Section: Methodsmentioning

confidence: 99%

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Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer

et al. 2019

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Delivery of nucleic acids into solid tumor environments remains a pressing challenge. This study examines the ability of macrophages to horizontally transfer small interfering RNA (siRNA) lipoplexes to cancer cells. Macrophages are a natural candidate for a drug carrier because of their ability to accumulate at high densities into many cancer types, including, breast, prostate, brain, and colon cancer. Here, it is demonstrated that macrophages can horizontally transfer siRNA to cancer cells during in vitro coculture. The amount of transfer can be dosed depending on the amount of siRNA loaded and total number of macrophages delivered. Macrophages loaded with calcium integrin binding protein‐1 (CIB1)‐siRNA result in decreased tumorsphere growth and decreased mRNA expression of CIB1 and KI67 in MDA‐MB‐468 human breast cancer cells. Adoptive transfer of macrophages transfected with CIB1‐siRNA localizes to the orthotopic MDA‐MB‐468 tumor. Furthermore, it is reported that macrophage activation can modulate this transfer process as well as intracellular trafficking protein Rab27a. As macrophages are heavily involved in tumor progression, understanding how to use macrophages for drug delivery can substantially benefit the treatment of tumors.

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Section: Methodsmentioning

confidence: 99%

“…Cationic siRNA lipoplexes are beneficial packaging systems for nonviral siRNA delivery. [12][13][14] Cationic lipids form complexes with negatively charged siRNA via electrostatic interaction. [15,16] Optimization of the complex formation parameters (such as lipid composition, ratio to siRNA, mixing temperature, etc.)…”

Section: Introductionmentioning

confidence: 99%

Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer

et al. 2019

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“…However, they suffer from relatively low loading capacity for siRNA and premature leakage of payloads, and they require additional cationic materials to condense the highly anionic payloads into the liposomal core. Commonly used condensers include protamine, peptides, and polyethylenimine (PEI) …”

Section: Protective Carriers For Sirna Deliverymentioning

confidence: 99%

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

2019

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The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201903637.With the recent FDA approval of the first siRNA-derived therapeutic, RNA interference (RNAi)-mediated gene therapy is undergoing a transition from research to the clinical space. The primary obstacle to realization of RNAi therapy has been the delivery of oligonucleotide payloads. Therefore, the main aims is to identify and describe key design features needed for nanoscale vehicles to achieve effective delivery of siRNA-mediated gene silencing agents in vivo. The problem is broken into three elements: 1) protection of siRNA from degradation and clearance; 2) selective homing to target cell types; and 3) cytoplasmic release of the siRNA payload by escaping or bypassing endocytic uptake. The in vitro and in vivo gene silencing efficiency values that have been reported in publications over the past decade are quantitatively summarized by material type (lipid, polymer, metal, mesoporous silica, and porous silicon), and the overall trends in research publication and in clinical translation are discussed to reflect on the direction of the RNAi therapeutics field.

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“…Plasmid and DNA isolation/purification kits were purchased from TIANGEN Biotech Co., Ltd. (Beijing, China). Transfection reagent DoGOX was described in our previvors study (Ganbold et al, 2017). 293T cells were propagated in Dulbecco's modified Eagle medium (DMEM) (HyClone, USA) supplemented with 10% fetal bovine serum (Gibco, USA) and maintained in a humidified incubator at 37°C with 5% CO2.…”

Section: In Vitro Transfection Of Psars-cov-2-s Plasmidmentioning

confidence: 99%

Oral delivery of SARS-CoV-2 DNA vaccines using attenuatedSalmonella typhimuriumas a carrier in rat

Yang

Zhu

Meng

et al. 2020

Preprint

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The 2019 novel coronavirus disease (COVID-19) is the disease that has been identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the prophylactic treatment of SARS-CoV-2 is still under investigation. The effective delivery of eukaryotic expression plasmids to the immune system’s inductive cells constitutes an essential requirement for the generation of effective DNA vaccines. Here, we have explored the use of Salmonella typhimurium as vehicles to deliver expression plasmids orally. Attenuated Salmonella phoP harboring eukaryotic expression plasmids that encoded spike protein of SARS-CoV-2 was administered orally to Wistar rats. Rats were immunized orally with Salmonella that carried a eukaryotic expression plasmid once a week for three consecutive weeks. The efficiency of the vaccination procedure was due to the transfer of the expression plasmid from the bacterial carrier to the mammalian host. Evidence for such an event could be obtained in vivo and in vitro. Our results showed that all immunized animals generated humoral immunity against the SARS-CoV-2 spike protein, indicating that a Salmonella-based vaccine carrying the Spike gene can elicit SARS-CoV-2-specific humoral immune responses in rats, and may be useful for the development of a protective vaccine against SARS-CoV-2 infection.

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Efficient in vivo siRNA delivery by stabilized d-peptide-based lipid nanoparticles

Abstract: A lipid functionalized d-dipeptide has shown remarkable biocompatibility and tissue targeting as well as excellent RNAi delivery efficiency in vivo.

Cited by 12 publications

References 30 publications

Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer

Targeted Delivery of siRNA Lipoplexes to Cancer Cells Using Macrophage Transient Horizontal Gene Transfer

Rekindling RNAi Therapy: Materials Design Requirements for In Vivo siRNA Delivery

Oral delivery of SARS-CoV-2 DNA vaccines using attenuatedSalmonella typhimuriumas a carrier in rat

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