Unmethylated CpG motifs are prevalent in bacterial but not vertebrate genomic DNAs. Oligodeoxynucleotides (ODN) containing CpG motifs activate host defense mechanisms leading to innate and acquired immune responses. The recognition of CpG motifs requires Toll-like receptor (TLR) 9, which triggers alterations in cellular redox balance and the induction of cell signaling pathways including the mitogen activated protein kinases (MAPKs) and NF kappa B. Cells that express TLR-9, which include plasmacytoid dendritic cells (PDCs) and B cells, produce Th1-like proinflammatory cytokines, interferons, and chemokines. Certain CpG motifs (CpG-A) are especially potent at activating NK cells and inducing IFN-alpha production by PDCs, while other motifs (CpG-B) are especially potent B cell activators. CpG-induced activation of innate immunity protects against lethal challenge with a wide variety of pathogens, and has therapeutic activity in murine models of cancer and allergy. CpG ODN also enhance the development of acquired immune responses for prophylactic and therapeutic vaccination.

CpG Motifs in Bacterial DNA and Their Immune Effects

RNA interference (RNAi) holds considerable promise as a therapeutic approach to silence disease-causing genes, particularly those that encode so-called 'non-druggable' targets that are not amenable to conventional therapeutics such as small molecules, proteins, or monoclonal antibodies. The main obstacle to achieving in vivo gene silencing by RNAi technologies is delivery. Here we show that chemically modified short interfering RNAs (siRNAs) can silence an endogenous gene encoding apolipoprotein B (apoB) after intravenous injection in mice. Administration of chemically modified siRNAs resulted in silencing of the apoB messenger RNA in liver and jejunum, decreased plasma levels of apoB protein, and reduced total cholesterol. We also show that these siRNAs can silence human apoB in a transgenic mouse model. In our in vivo study, the mechanism of action for the siRNAs was proven to occur through RNAi-mediated mRNA degradation, and we determined that cleavage of the apoB mRNA occurred specifically at the predicted site. These findings demonstrate the therapeutic potential of siRNAs for the treatment of disease.

Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs

Construction of improved M13 vectors using oligodeoxynucleotide-directed mutagenesis.

III. Foldamer Research 3910 A. Overview 3910 B. Motivation 3910 C. Methods 3910 D. General Scope 3912 IV. Peptidomimetic Foldamers 3912 A. The R-Peptide Family 3913 1. Peptoids 3913 2. N,N-Linked Oligoureas 3914 3. Oligopyrrolinones 3915 4. Oxazolidin-2-ones 3916 5. Azatides and Azapeptides 3916 B. The â-Peptide Family 3917 1. â-Peptide Foldamers 3917 2. R-Aminoxy Acids 3937 3. Sulfur-Containing â-Peptide Analogues 3937 4. Hydrazino Peptides 3938 C. The γ-Peptide Family 3938 1. γ-Peptide Foldamers 3938 2. Other Members of the γ-Peptide Family 3941 D. The δ-Peptide Family 3941 1. Alkene-Based δ-Amino Acids 3941 2. Carbopeptoids 3941 V. Single-Stranded Abiotic Foldamers 3944 A. Overview 3944 B. Backbones Utilizing Bipyridine Segments 3944 1. Pyridine−Pyrimidines 3944 2. Pyridine−Pyrimidines with Hydrazal Linkers 3945

A field guide to foldamers.

The partial amino-acid sequence of purified human transforming growth factor-beta (TGF-beta) was used to identify a series of cDNA clones encoding the protein. The cDNA sequence indicates that the 112-amino acid monomeric form of the natural TGF-beta homodimer is derived proteolytically from a much longer precursor polypeptide which may be secreted. TGF-beta messenger RNA is synthesized in various normal and transformed cells.

/pdf/human-transforming-growth-factor-beta-complementary-dna-16zn58cf34.pdf

Human transforming growth factor-beta complementary DNA sequence and expression in normal and transformed cells.

Publisher Summary This chapter discusses the chemical synthesis of deoxy oligonucleotides by the phosphoramidite method. It discusses the synthesis methodology; detailed protocols for preparing the silica support, the phosphoramidite, and deoxy oligonucleotides; and the purification of synthetic deoxyribo nucleic acid (DNA). The phosphite triester approach to DNA synthesis using deoxynucleoside phosphoramidite as synthons has become the method of choice for the preparation of deoxy oligonucleotides. The general synthetic strategy involves adding mononucleotides sequentially to a deoxynucleoside, attached covalently to a silica-based insoluble polymeric support. Reagents, starting materials, and side products are then removed simply by filtration. At the conclusion of the synthesis, the deoxy oligonucleotide is chemically freed of blocking groups, hydrolyzed from the support, and purified to homogeneity by either polyacrylamide gel electrophoresis (PAGE) or high-performance liquid chromatography (HPLC). These preformed synthons are especially attractive for preparing DNA on automatic or semiautomatic DNA synthesizers, or for those who plan to manually synthesize a large number of deoxy oligonucleotides.

Chemical synthesis of deoxyoligonucleotides by the phosphoramidite method.

3H-1,2-Benzodithiole-3-one 1,1-dioxide as an improved sulfurizing reagent in the solid-phase synthesis of oligodeoxyribonucleoside phosphorothioates

A new class of nucleoside phosphoramidites which are relatively stable to permit isolation thereof and storage at room temperature. The phosphoramidites are derivatives of saturated secondary amines.

Process for oligonucleotide synthesis using phosphoramidite intermediates

https://zenodo.org/record/1259711/files/article.pdf

Serge L. Beaucage

Papers

Chemical synthesis of deoxyoligonucleotides by the phosphoramidite method.

3H-1,2-Benzodithiole-3-one 1,1-dioxide as an improved sulfurizing reagent in the solid-phase synthesis of oligodeoxyribonucleoside phosphorothioates

Process for oligonucleotide synthesis using phosphoramidite intermediates

The Functionalization of Oligonucleotides Via Phosphoramidite Derivatives

Phosphoramidite nucleoside compounds