Is it Time for Multi-Drug Therapy with Combination of Therapeutic Nucleic Acids?

Therapeutic nucleic acids (TNAs) are a new class of drugs that exhibit different properties and mechanisms of action from those of small molecules or biological drugs. Over twenty oligonucleotide drugs and several COVID-19 vaccines have received regulatory approval for clinical use. A characteristic feature of these TNAs is that they are directed against one specific biological target and one specific RNA or DNA sequence.

Quantum Chemical and Biological Insights into Redox Activity of Metallacarborane Complexes in Cancer Cells.

A relationship between the electronic properties of metal ions in metallacarboranes and their ability to modulate mitochondrial oxidase activity and membrane hyperpolarization in cancer cells was demonstrated. Quantum chemistry methods, including DFT and molecular dynamics simulations, were used to understand the oxidized and reduced forms of metallacarboranes and their intramolecular rotatory behavior. According to the low-spin assumption for metal ions, the intramolecular oscillations of cluster ligands in metallacarboranes are significantly influenced by the type of metal and correspond to the cellular uptake of these complexes .

Early Stage In Vitro Bioprofiling of Potential Low-Molecular-Weight Organoboron Compounds for Boron Neutron Capture Therapy (BNCT)-Proposal for a Guide.

Given the renewed interest in boron neutron capture therapy (BNCT) and the intensified search for improved boron carriers, as well as the difficulties of coherently comparing the carriers described so far, it seems necessary to define a basic set of assays and standardized methods to be used in the early stages of boron carrier development in vitro. The selection of assays and corresponding methods is based on the practical experience of the authors and is certainly not exhaustive, but open to discussion. The proposed tests/characteristics: Solubility, lipophilicity, stability, cytotoxicity, and cellular uptake apply to both low molecular weight (up to 500 Da) and high molecular weight (5000 Da and more) boron carriers.

Synthesis of DNA-Boron Cluster Composites and Assembly into Functional Nanoparticles with Dual, Anti-EGFR, and Anti-c-MYC Oncogene Silencing Activity.

A versatile method for the automated synthesis of composites containing DNA-oligonucleotides and boron cluster scaffolds and their assembly into functional nanoparticles is described. The obtained, torus-like nanoparticles carry antisense oligonucleotides that target two different oncogenes simultaneously. The nanoparticles exhibited notable silencing efficiency in vitro in a pancreatic carcinoma cell line PANC-1 toward EGFR and c-Myc genes at the mRNA level, and a significant efficiency at the protein level.

Normalized Multipotential Redox Coding of DNA Bases for Determination of Total Nucleotide Composition.

The previously reported approach of orthogonal multipotential redox coding of all four DNA bases allowed only analysis of the relative nucleotide composition of short DNA stretches. Here, we present two methods for normalization of the electrochemical readout to facilitate the determination of the total nucleotide composition. The first method is based on the presence or absence of an internal standard of 7-deaza-2'-deoxyguanosine in a DNA primer.