A new method for the ablation of undesirable tissue such as cells of a cancerous or non-cancerous tumor is disclosed. It involves the placement of electrodes into or near the vicinity of the undesirable tissue through the application of electrical pulses causing irreversible electroporation of the cells throughout the entire area of the undesirable tissue. The electric pulses irreversibly permeate the cell membranes, thereby invoking cell death. The irreversibly permeabilized cells are left in situ and are removed by the body immune system. The amount of tissue ablation achievable through the use of irreversible electroporation without inducing thermal damage is considerable.

Tissue ablation with irreversible electroporation

Macrophages handle extracellular proteins and secrete diverse bioactive molecules and, therefore, influence the physiology of many tissues. They also have an important immunoregulatory role. The immune response to proteins involves the activation of the T helper subset of lymphocytes. The T helper cell is activated only when it interacts with the protein displayed on the surface of a macrophage or other accessory cell. This interaction involves restrictive proteins encoded in the major histocompatibility gene complex as well as growth-differentiating proteins.

https://science.sciencemag.org/content/sci/236/4801/551.full.pdf

The basis for the immunoregulatory role of macrophages and other accessory cells.

The success of gene therapy is largely dependent on the development of the gene delivery vector. Recently, gene transfection into target cells using naked DNA, which is a simple and safe approach, has been improved by combining several physical techniques, for example, electroporation, gene gun, ultrasound and hydrodynamic pressure. Chemical approaches have been utilized to improve the efficiency and cell specificity of gene transfer. Novel gene carrier molecules, which facilitate DNA escape from the endosome into the cytosol, have been developed. Several functional polymers, which enable controlled release of DNA in response to an environmental change, have also been reported. Plasmids with reduced number of CpG motifs, the use of PCR fragments and the sequential injection method have been established for the reduction of immune response triggered by plasmid DNA. Construction of a long-lasting gene expression system is also an important theme for nonviral gene therapy. To date, tissue-specific expression, self-replicating and integrating plasmid systems have been reported. Improvement of delivery methods together with intelligent design of the DNA itself has brought about large degrees of enhancement in the efficiency, specificity and temporal control of nonviral vectors.

/pdf/gene-therapy-progress-and-prospects-nonviral-vectors-ab14ym091g.pdf

Gene therapy progress and prospects: nonviral vectors.

Methods and apparatus are provided for renal neuromodulation using a pulsed electric field to effectuate electroporation or electrofusion. It is expected that renal neuromodulation (e.g., denervation) may, among other things, reduce expansion of an acute myocardial infarction, reduce or prevent the onset of morphological changes that are affiliated with congestive heart failure, and/or be efficacious in the treatment of end stage renal disease. Embodiments of the present invention are configured for percutaneous intravascular delivery of pulsed electric fields to achieve such neuromodulation.

Methods and apparatus for renal neuromodulation

A surgical device comprising a container and a tether used for delivering a sterile appliance into a body cavity during endoscopic procedures. Once positioned in the body cavity, a force is applied to the container through the tether. The force opens the container and releases the sterile appliance into the body cavity. In various embodiments, gas or liquid may be used to open the container.

Sterile appliance delivery device for endoscopic procedures

DNA vaccines have been demonstrated to be potent in small animals but are less effective in primates. One limiting factor may be inefficient uptake of DNA by cells in situ. In this study, we evaluated whether cellular uptake of DNA was a significant barrier to efficient transfection in vivo and subsequent induction of immune responses. For this purpose, we used the technique of electroporation to facilitate DNA delivery in vivo. This technology was shown to substantially increase delivery of DNA to cells, resulting in increased expression and elevated immune responses. The potency of a weakly immunogenic hepatitis B surface Ag DNA vaccine was increased in mice, as seen by a more rapid onset and higher magnitude of anti-hepatitis B Abs. In addition, the immunogenicity of a potent HIV gag DNA vaccine was increased in mice, as seen by higher Ab titers, a substantial reduction in the dose of DNA required to induce an Ab response, and an increase in CD8+ T cell responses. Finally, Ab responses were enhanced by electroporation against both components of a combination HIV gag and env DNA vaccine in guinea pigs and rabbits. Therefore, cellular uptake of DNA is a significant barrier to transfection in vivo, and electroporation appears able to overcome this barrier.

/pdf/increased-dna-vaccine-delivery-and-immunogenicity-by-d7pjduwkl2.pdf

Increased DNA vaccine delivery and immunogenicity by electroporation in vivo.

The present invention describes an in vivo method, using pulsed electric field to deliver therapeutic agents into cells of the skin and muscle for local and systemic treatments. In particular, therapeutic agents include naked or formulated nucleic acid, polypeptides and chemotherapeutic agents.

Skin and muscle-targeted gene therapy by pulsed electrical field

Enhancement of DNA vaccine potency in rhesus macaques by electroporation

Transgenic mice selectively lacking MHC class II (I-E) antigen expression on B cells: An in vivo approach to investigate la gene function

In vivo methods are provided for using an electric field to delivery therapeutic treatment to a subject while reducing inducement of histopathological change in the target muscle tissue, such as is associated with induction or amplification of an immune response caused by the pulsed electric field. Therapeutic agents can be delivered nto cells of muscle for local and systemic treatments with optimal gene expression and minimal tissue damage. In particular, therapeutic agents include naked or formulated nucleic acid, polypeptides and chemotherapeutic agents.

Georg Widera

Papers

Increased DNA vaccine delivery and immunogenicity by electroporation in vivo.

Skin and muscle-targeted gene therapy by pulsed electrical field

Enhancement of DNA vaccine potency in rhesus macaques by electroporation

Transgenic mice selectively lacking MHC class II (I-E) antigen expression on B cells: An in vivo approach to investigate la gene function

Electrical field therapy with reduced histopathological change in muscle