Transfer of small interfering RNA by electropermeabilization in tumor spheroids.

The ability to modulate deregulated genes by RNAi provides treatment perspectives in certain diseases including cancers. Electrotransfer of oligonucleotides was studied in vitro, showing a direct transfer of negatively charged siRNA across the plasma membrane into the cytoplasm. In vivo, the feasibility of siRNA electrotransfer was demonstrated in different studies and tissues.

Morniga-G, a T/Tn-Specific Lectin, Induces Leukemic Cell Death via Caspase and DR5 Receptor-Dependent Pathways.

Morniga-G, the Gal-specific black mulberry () lectin, displays high affinity for T (CD176) and Tn (CD175) antigens, frequently expressed at the cancer cell surface. The effects of Morniga-G were investigated on a Tn-positive leukemic Jurkat cell line. The lectin, used in a concentration range between 5⁻20 μg/mL, induced cell death in leukemic Jurkat cells.

DNA polymerase ν gene expression influences fludarabine resistance in chronic lymphocytic leukemia independently of p53 status.

Alteration in the DNA replication, repair or recombination processes is a highly relevant mechanism of genomic instability. Despite genomic aberrations manifested in hematologic malignancies, such a defect as a source of biomarkers has been underexplored. Here, we investigated the prognostic value of expression of 82 genes involved in DNA replication-repair-recombination in a series of 99 patients with chronic lymphocytic leukemia without detectable 17p deletion or mutation.

Increased permeability of blood vessels after reversible electroporation is facilitated by alterations in endothelial cell-to-cell junctions.

Delivery of electric field pulses, i.e. electroporation (EP), to tissues has been shown to have a blood flow modifying effect.

Analysis of DNA Replication by Optical Mapping in Nanochannels.

DNA replication is essential to maintain genome integrity in S phase of the cell division cycle. Accumulation of stalled replication forks is a major source of genetic instability, and likely constitutes a key driver of tumorigenesis. The mechanisms of regulation of replication fork progression have therefore been extensively investigated, in particular with DNA combing, an optical mapping technique that allows the stretching of single molecules and the mapping of active region for DNA synthesis by fluorescence microscopy.

Delivery of RNAi-Based Oligonucleotides by Electropermeabilization.

For more than a decade, understanding of RNA interference (RNAi) has been a growing field of interest. The potent gene silencing ability that small oligonucleotides have offers new perspectives for cancer therapeutics. One of the present limits is that many biological barriers exist for their efficient delivery into target cells or tissues.

Intravital microscopy at the single vessel level brings new insights of vascular modification mechanisms induced by electropermeabilization.

Electroporation/electropermeabilization, i.e. the result of the application of electric pulses to tissues, is a physical method for delivery of exogenous molecules into cells.

Chemically modified oligonucleotide-increased stability negatively correlates with its efficacy despite efficient electrotransfer.

Despite great potential for disease treatment, small interfering RNA (siRNA) development has been hampered due to its poor stability and the lack of efficient delivery method. To overcome the sensitivity, new generations of chemically modified oligonucleotides have been developed such as the locked nucleic acid (LNA). LNA substitution in an siRNA sequence (siLNA) is supposed to increase its stability and its affinity for its complementary sequence.

In vivo molecular imaging and histological analysis of changes induced by electric pulses used for plasmid DNA electrotransfer to the skin: a study in a dorsal window chamber in mice.

Electropermeabilization/electroporation (EP) is a physical method that by application of electric pulses to cells increases cell membrane permeability and enables the introduction of molecules into the cells. One of the uses of EP in vivo is plasmid DNA electrotransfer to the skin for DNA vaccination. EP of tissues induces reduction of blood flow and, in combination with plasmid DNA, induction of an immune response.

Electrotransfer of RNAi-based oligonucleotides for oncology.

For more than a decade, there has been tremendous growth in our understanding of RNA interference (RNAi). The potent ability that small oligonucleotides have in gene silencing makes them desirable as novel cancer therapeutics, but many biological barriers exist for their efficient delivery into target cells or tissues. Electropulsation (EP) appears to be a promising method for cancer-associated gene therapy.