Oligonucleotides 

About: Oligonucleotides is an academic journal. The journal publishes majorly in the area(s): RNA & Oligonucleotide. It has an ISSN identifier of 1545-4576. Over the lifetime, 276 publications have been published receiving 9266 citations.

Analysis of thermal melting curves

Abstract: Tm is defined as Temperature of melting or, more accurately, as temperature of midtransition. This term is often used for nucleic acids (DNA and RNA, oligonucleotides and polynucleotides). A thermal denaturation experiment determines the stability of the secondary structure of a DNA or RNA and aids in the choice of the sequences for antisense oligomers or PCR primers. Beyond a simple numerical value (the Tm), a thermal denaturation experiment, in which the folded fraction of a structure is plotted vs. temperature, yields important thermodynamic information. We present the classic problems encountered during these experiments and try to demonstrate that a number of useful pieces of information can be extracted from these experimental curves.

Chemical Modification of siRNAs for In Vivo Use

Abstract: Well over a hundred reports have been published describing use of synthetic small-interfering RNAs (siRNAs) in animals. The majority of these reports employed unmodified RNA duplexes. While unmodified RNA is the natural effector molecule of RNA interference, certain problems arise with experimental or therapeutic use of RNA duplexes in vivo, some of which can be improved or solved through use of chemical modifications. Judicious use of chemical modifications can improve the nuclease stability of an RNA duplex, decrease the likelihood of triggering an innate immune response, lower the incidence of off-target effects (OTEs), and improve pharmacodynamics. This review will examine studies that document the utility of various chemical modifications for use in siRNAs, both in vitro and in vivo, with close attention given to reports demonstrating actual performance in animal model systems.

siRNA and innate immunity.

Abstract: Canonical small interfering RNA (siRNA) duplexes are potent activators of the mammalian innate immune system. The induction of innate immunity by siRNA is dependent on siRNA structure and sequence, method of delivery, and cell type. Synthetic siRNA in delivery vehicles that facilitate cellular uptake can induce high levels of inflammatory cytokines and interferons after systemic administration in mammals and in primary human blood cell cultures. This activation is predominantly mediated by immune cells, normally via a Toll-like receptor (TLR) pathway. The siRNA sequence dependency of these pathways varies with the type and location of the TLR involved. Alternatively nonimmune cell activation may also occur, typically resulting from siRNA interaction with cytoplasmic RNA sensors such as RIG1. As immune activation by siRNA-based drugs represents an undesirable side effect due to the considerable toxicities associated with excessive cytokine release in humans, understanding and abrogating this activity will ...

Locked nucleic acid: a potent nucleic acid analog in therapeutics and biotechnology.

Abstract: Locked nucleic acid (LNA) is a class of nucleic acid analogs possessing very high affinity and excellent specificity toward complementary DNA and RNA, and LNA oligonucleotides have been applied as antisense molecules both in vitro and in vivo. In this review, we briefly describe the basic physiochemical properties of LNA and some of the difficulties that may be encountered when applying LNA technology. The central part of the review focuses on the use of LNA molecules in regulation of gene expression, including delivery to cells, stability, unspecific effects, toxicity, pharmacokinetics, and design of LNA oligonucleotides. The last part evaluates LNA as a diagnostic tool in genotyping.

Inhibition of TGF-beta2 with AP 12009 in recurrent malignant gliomas: from preclinical to phase I/II studies.

Abstract: Transforming growth factor-beta2 (TGF-beta2) is known to suppress the immune response to cancer cells and plays a pivotal role in tumor progression by regulating key mechanisms including proliferation, metastasis, and angiogenesis. For targeted protein suppression the TGF-beta2-specific antisense oligodeoxynucleotide AP 12009 was developed. In vitro experiments have been performed to prove specificity and efficacy of the TGF-beta2 inhibitor AP 12009 employing patient-derived malignant glioma cells as well as peripheral blood mononuclear cells (PBMCs) from patients. Clinically, the antisense compound AP 12009 was assessed in three Phase I/II-studies for the treatment of patients with recurrent or refractory malignant (high-grade) glioma WHO grade III or IV. Although the study was not primarily designed as an efficacy evaluation, prolonged survival compared to literature data and response data were observed, which are very rarely seen in this tumor indication. Two patients experienced long-lasting complete tumor remissions. These results implicate targeted TGF-beta2-suppression using AP 12009 as a promising novel approach for malignant gliomas and other highly aggressive, TGF-beta-2-overexpressing tumors.