Triazole- and Tetrazole-Bridged Nucleic Acids: Synthesis, Duplex Stability, Nuclease Resistance, and in Vitro and in Vivo Antisense Potency

2016 ◽  
Vol 82 (1) ◽  
pp. 12-24 ◽  
Author(s):  
Yasunori Mitsuoka ◽  
Tsuyoshi Yamamoto ◽  
Akira Kugimiya ◽  
Reiko Waki ◽  
Fumito Wada ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Duplex Stability ◽  
Nuclease Resistance

Amido-Bridged Nucleic Acids (AmNAs): Synthesis, Duplex Stability, Nuclease Resistance, and in Vitro Antisense Potency

ChemBioChem ◽  
2012 ◽  
Vol 13 (17) ◽  
pp. 2513-2516 ◽  
Author(s):  
Aiko Yahara ◽  
Ajaya Ram Shrestha ◽  
Tsuyoshi Yamamoto ◽  
Yoshiyuki Hari ◽  
Takashi Osawa ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Duplex Stability ◽  
Nuclease Resistance

Exosome as a Natural Gene Delivery Vector for Cancer Treatment

2020 ◽  
Vol 20 (11) ◽  
pp. 821-830
Author(s):  
Prasad Pofali ◽  
Adrita Mondal ◽  
Vaishali Londhe
Keyword(s):  
Gene Therapy ◽  
Gene Delivery ◽  
Nucleic Acids ◽  
Cancer Treatment ◽  
Intestinal Barrier ◽  
Gene Carrier ◽  
Gene Delivery Vector ◽  
Delivery Vector

Background: Current gene therapy vectors such as viral, non-viral, and bacterial vectors, which are used for cancer treatment, but there are certain safety concerns and stability issues of these conventional vectors. Exosomes are the vesicles of size 40-100 nm secreted from multivesicular bodies into the extracellular environment by most of the cell types in-vivo and in-vitro. As a natural nanocarrier, exosomes are immunologically inert, biocompatible, and can cross biological barriers like the blood-brain barrier, intestinal barrier, and placental barrier. Objective: This review focusses on the role of exosome as a carrier to efficiently deliver a gene for cancer treatment and diagnosis. The methods for loading of nucleic acids onto the exosomes, advantages of exosomes as a smart intercellular shuttle for gene delivery and therapeutic applications as a gene delivery vector for siRNA, miRNA and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and also the limitations of exosomes as a gene carrier are all reviewed in this article. Methods: Mostly, electroporation and chemical transfection are used to prepare gene loaded exosomes. Results: Exosome-mediated delivery is highly promising and advantageous in comparison to the current delivery methods for systemic gene therapy. Targeted exosomes, loaded with therapeutic nucleic acids, can efficiently promote the reduction of tumor proliferation without any adverse effects. Conclusion: In the near future, exosomes can become an efficient gene carrier for delivery and a biomarker for the diagnosis and treatment of cancer.

scholarly journals Novel PEGylated Liposomes Enhance Immunostimulating Activity of isRNA

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3101 ◽  
Author(s):  
Tatyana Kabilova ◽  
Elena Shmendel ◽  
Daniil Gladkikh ◽  
Nina Morozova ◽  
Mikhail Maslov ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Cationic Liposomes ◽  
Circulation Time ◽  
Target Cells ◽  
Immunostimulating Activity ◽  
Pegylated Liposomes ◽  
Liposome Preparation ◽  
Molecular Masses

The performance of cationic liposomes for delivery of therapeutic nucleic acids in vivo can be improved and specifically tailored to certain types of cargo and target cells by incorporation of PEG-containing lipoconjugates in the cationic liposome’s composition. Here, we report on the synthesis of novel PEG-containing lipoconjugates with molecular masses of PEG 800, 1500 and 2000 Da. PEG-containing lipoconjugates were used as one of the components in liposome preparation with the polycationic amphiphile 1,26-bis(cholest-5-en-3β-yloxycarbonylamino)-7,11,16,20-tetra-azahexacosan tetrahydrochloride (2X3) and the lipid-helper dioleoylphosphatidylethanolamine (DOPE). We demonstrate that increasing the length of the PEG chain reduces the transfection activity of liposomes in vitro, but improves the biodistribution, increases the circulation time in the bloodstream and enhances the interferon-inducing activity of immunostimulating RNA in vivo.

scholarly journals Triple-Helical DNA in Drosophila Heterochromatin

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 227 ◽  
Author(s):  
Eduardo Gorab
Keyword(s):  
Nucleic Acids ◽  
Dna Sequences ◽  
Detection Methods ◽  
Triplex Dna ◽  
Thiazole Orange ◽  
Chromosomal Dna ◽  
Mitotic Chromosomes ◽  
Satellite Repeats

Polynucleotide chains obeying Watson-Crick pairing are apt to form non-canonical complexes such as triple-helical nucleic acids. From early characterization in vitro, their occurrence in vivo has been strengthened by increasing evidence, although most remain circumstantial particularly for triplex DNA. Here, different approaches were employed to specify triple-stranded DNA sequences in the Drosophila melanogaster chromosomes. Antibodies to triplex nucleic acids, previously characterized, bind to centromeric regions of mitotic chromosomes and also to the polytene section 59E of mutant strains carrying the brown dominant allele, indicating that AAGAG tandem satellite repeats are triplex-forming sequences. The satellite probe hybridized to AAGAG-containing regions omitting chromosomal DNA denaturation, as expected, for the intra-molecular triplex DNA formation model in which single-stranded DNA coexists with triplexes. In addition, Thiazole Orange, previously described as capable of reproducing results obtained by antibodies to triple-helical DNA, binds to AAGAG repeats in situ thus validating both detection methods. Unusual phenotype and nuclear structure exhibited by Drosophila correlate with the non-canonical conformation of tandem satellite arrays. From the approaches that lead to the identification of triple-helical DNA in chromosomes, facilities particularly provided by Thiazole Orange use may broaden the investigation on the occurrence of triplex DNA in eukaryotic genomes.

scholarly journals Two Antibody-Guided Lactic-co-Glycolic Acid-Polyethylenimine (LGA-PEI) Nanoparticle Delivery Systems for Therapeutic Nucleic Acids

2021 ◽  
Vol 14 (9) ◽  
pp. 841
Author(s):  
Jian-Ming Lü ◽  
Zhengdong Liang ◽  
Dongliang Liu ◽  
Bin Zhan ◽  
Qizhi Yao ◽  
...  
Keyword(s):  
Nucleic Acids ◽  
Plasmid Dna ◽  
Glycolic Acid ◽  
Growth Factor Receptor ◽  
Green Fluorescence Protein ◽  
Active Targeting ◽  
Single Chain ◽  
Targeting Delivery

We previously reported a new polymer, lactic-co-glycolic acid-polyethylenimine (LGA-PEI), as an improved nanoparticle (NP) delivery for therapeutic nucleic acids (TNAs). Here, we further developed two antibody (Ab)-conjugated LGA-PEI NP technologies for active-targeting delivery of TNAs. LGA-PEI was covalently conjugated with a single-chain variable fragment antibody (scFv) against mesothelin (MSLN), a biomarker for pancreatic cancer (PC), or a special Ab fragment crystallizable region-binding peptide (FcBP), which binds to any full Ab (IgG). TNAs used in the current study included tumor suppressor microRNA mimics (miR-198 and miR-520h) and non-coding RNA X-inactive specific transcript (XIST) fragments; green fluorescence protein gene (GFP plasmid DNA) was also used as an example of plasmid DNA. MSLN scFv-LGA-PEI NPs with TNAs significantly improved their binding and internalization in PC cells with high expression of MSLN in vitro and in vivo. Anti-epidermal growth factor receptor (EGFR) monoclonal Ab (Cetuximab) binding to FcBP-LGA-PEI showed active-targeting delivery of TNAs to EGFR-expressing PC cells.

REGULATION OF THE METABOLISM OF PITUITARY NUCLEIC ACIDS IN FEMALE RATS

1980 ◽  
Vol 85 (1) ◽  
pp. 1-8 ◽  
Author(s):  
J. BÍRÓ
Keyword(s):  
Nucleic Acids ◽  
Intraperitoneal Injection ◽  
Anterior Pituitary ◽  
Rna Metabolism ◽  
Female Rats ◽  
Biphasic Effect ◽  
Lh Rh ◽  
Lh Releasing Hormone

SUMMARY Ovariectomy caused an increase in the metabolism of pituitary nucleic acids. This effect was reversed in vivo by a biphasic action of oestradiol-17β which first facilitated RNA metabolism after 8 h and then inhibited it 16 h after intraperitoneal injection. To analyse the origin of this biphasic effect the roles of LH releasing hormone (LH-RH) and hysterectomy were examined. Incorporation of uridine into the RNA of the anterior pituitary gland of female rats was inhibited both in vivo and in vitro by LH-RH. Hysterectomy augmented the increase in the RNA metabolism caused by ovariectomy whereas steroid-free uterine extracts inhibited the increase significantly. We have concluded that extrapituitary factors may be involved in the effects of oestrogen on the metabolism of pituitary nucleic acids.

scholarly journals Mesyl phosphoramidate backbone modified antisense oligonucleotides targeting miR-21 with enhanced in vivo therapeutic potency

2020 ◽  
Vol 117 (51) ◽  
pp. 32370-32379
Author(s):  
Olga A. Patutina ◽  
Svetlana K. Gaponova (Miroshnichenko) ◽  
Aleksandra V. Sen’kova ◽  
Innokenty A. Savin ◽  
Daniil V. Gladkikh ◽  
...  
Keyword(s):  
Tumor Model ◽  
Rnase H ◽  
Mouse Tumor ◽  
Internal Organs ◽  
Potent Inhibition ◽  
Nuclease Resistance ◽  
New Type

The design of modified oligonucleotides that combine in one molecule several therapeutically beneficial properties still poses a major challenge. Recently a new type of modified mesyl phosphoramidate (or µ-) oligonucleotide was described that demonstrates high affinity to RNA, exceptional nuclease resistance, efficient recruitment of RNase H, and potent inhibition of key carcinogenesis processes in vitro. Herein, using a xenograft mouse tumor model, it was demonstrated that microRNA miR-21–targeted µ-oligonucleotides administered in complex with folate-containing liposomes dramatically inhibit primary tumor growth via long-term down-regulation of miR-21 in tumors and increase in biosynthesis of miR-21–regulated tumor suppressor proteins. This antitumoral effect is superior to the effect of the corresponding phosphorothioate. Peritumoral administration of µ-oligonucleotide results in its rapid distribution and efficient accumulation in the tumor. Blood biochemistry and morphometric studies of internal organs revealed no pronounced toxicity of µ-oligonucleotides. This new oligonucleotide class provides a powerful tool for antisense technology.

scholarly journals THE USE OF BISMUTH AS AN ELECTRON STAIN FOR NUCLEIC ACIDS

1963 ◽  
Vol 17 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Peter Albersheim ◽  
Ursula Killias
Keyword(s):  
Nucleic Acids ◽  
Inorganic Phosphate ◽  
In Vitro Experiments ◽  
Root Tips ◽  
Onion Root ◽  
Cell Structures ◽  
Dividing Cells ◽  
Chromatin Material

Evidence is presented to show that bismuth combines in vitro with the phosphate of nucleic acids in a manner similar to its reaction with inorganic phosphate. When tested under similar conditions, protein exhibited no attraction for bismuth. The results of the in vitro experiments, which are of interest within themselves, may be indirectly applicable to in vivo staining. Dividing cells of onion root tips were fixed in OsO4, stained with bismuth, and examined in the electron microscope. The electron opacity of cell structures known to contain nucleic acids was enhanced by bismuth, while organelles known to lack appreciable quantities of DNA or RNA showed little, if any, change. Bismuth is particularly effective as a stain for the chromatin material during interphase and for the chromosomes during division.

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