Phosphodiester oligodeoxyribonucleotides linked to an intercalating agent or a dodecanol tail or both complementary to the 12th codon region of Ha-ras mRNA were compared with the unmodified oligonucleotides of the same size and sequence with respect to their ability to induce RNaseH cleavage and antisense activity in cell culture. The hydrophobic tail not only protected the oligonucleotide from nucleases but also enhanced RNase H cleavage of the target. Oligonucleotides carrying both an acridine and a dodecanol substituent inhibited the proliferation of HBL100ras1 cells (human mammary cells stably transformed with the T24 Ha-ras gene carrying a G-->T point mutation in codon 12) at a 20-fold to 30-fold lower concentration than unmodified ones. Therefore, these modified oligonucleotides may prove useful for antisense applications.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1089/oli.1.1997.7.361 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Peptide nucleic acids: Recent advancements and future opportunities in biomedical applications.
Bioorg Chem
January 2025
Department of Chemistry, Sarojini Naidu College for Women, Kolkata 700028, India. Electronic address:
Peptide nucleic acids (PNA), synthetic molecules comprising a peptide-like backbone and natural and unnatural nucleobases, have garnered significant attention for their potential applications in gene editing and other biomedical fields. The unique properties of PNA, particularly enhanced stability/specificity/affinity towards targeted DNA and RNA sequences, achieved significant attention recently for gene silencing, gene correction, antisense therapy, drug delivery, biosensing and other various diagnostic aspects. This review explores the structure, properties, and potential of PNA in transforming genetic engineering including potent biomedical challenges.
View Article and Find Full Text PDFHybrid prodrug nanoassembly for hypoxia-triggered immunogenic chemotherapy and immune modulation.
J Control Release
January 2025
Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China; NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, China; State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 210009, China. Electronic address:
Tumor hypoxia is a critical driver of cancer progression, metastasis, and therapy resistance, posing significant challenges in effective cancer treatment. Hypoxia-activable prodrugs offer a promising strategy to target tumors in low-oxygen conditions, but their efficacy is often hindered by intrinsic properties and extrinsic cues. In this study, we developed a dual-prodrug nanoassembly system (CPPA) composed of a hypoxia-triggerable camptothecin (CPT)-based dimeric prodrug (CP) and a lipid-conjugated STAT3 antisense oligonucleotide (ASO) prodrug (PA), aiming to enhance tumor-targeted chemotherapy and overcome the immune evasion within the tumor microenvironment.
View Article and Find Full Text PDFThe Influence of Length and Sequence of Complementary Oligonucleotides on the Spectral and Time-Resolved Fluorescence Properties of an H-Type Excitonic Dimer-Bearing Antisense Oligonucleotide.
J Phys Chem B
January 2025
OncoImmunin, Inc., 207A Perry Parkway, Suite 6, Gaithersburg, Maryland 20877, United States.
We have previously found that the presence of an H-type excitonic dimer formed by two fluorophores covalently bound to an oligonucleotide allows the delivery of such a polymer into live cells without inducing toxicity. We are now using time-resolved fluorescence measurements in solution to understand the molecular dynamics of an antisense probe and how pairing with complementary sense strands of various lengths and degrees of complementarity affects the antisense strand's properties. We report that a DNA strand composed of 30 residues and labeled with an H-type excitonic Cyanine-5/Cyanine-5 dimer shows a predominant 1.
View Article and Find Full Text PDFCells must limit RNA-RNA interactions to avoid irreversible RNA entanglement. Cells may prevent deleterious RNA-RNA interactions by genome organization to avoid complementarity however, RNA viruses generate long, perfectly complementary antisense RNA during replication. How do viral RNAs avoid irreversible entanglement? One possibility is RNA sequestration into biomolecular condensates.
View Article and Find Full Text PDFSelectively expressed RNA molecules as a versatile tool for functionalized cell targeting.
Nat Commun
January 2025
Institute of Biological Information Processing, IBI-2: Mechanobiology, Research Centre Juelich, Juelich, Germany.
Targeting of diseased cells is one of the most urgently needed prerequisites for a next generation of potent pharmaceuticals. Different approaches pursued fail mainly due to a lack of specific surface markers. Developing an RNA-based methodology, we can now ensure precise cell targeting combined with selective expression of effector proteins for therapy, diagnostics or cell steering.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!