Surgery – Instruments – Heat application
Reexamination Certificate
1998-12-22
2001-02-20
Peffley, Michael (Department: 3739)
Surgery
Instruments
Heat application
C606S031000, C607S101000
Reexamination Certificate
active
06190380
ABSTRACT:
BACKGROUND OF THE INVENTION
This invention relates to a cell treatment apparatus and method. More specifically, this invention relates to a treatment apparatus and method for transfecting a patient's cells in vivo.
Various techniques have been used, at least experimentally, for transfection of cells (i.e., insertion of new genetic material into the DNA structure of cells).
One technique for transfection of cells has used laser poration. This approach has been performed in vitro using a laser beam to porate a single cell at a time under a specially adapted microscope. The microscope allows the direct puncture of the cell membrane in the presence of the gene. Specifically, an operator directs the laser beam towards an individual cell and the puncture of the cell membrane allows genetic material on the same side as the cell to enter into the cell. This approach is labor intensive and not practical to use in vivo. This laser poration technique is described in the article by Tao et al. entitled “Direct Gene Transfer Into Human Cultured Cells Facilitated By Laser Micropuncture of Cell Membrane” in the Proceedings of the National Academy of Science in 1987; 84:4180-4184.
Other approaches to transfection of cells have included chemical methods or electrical poration used in a cell culture, but such methods have not been readily applicable in vivo. In other words, such methods may allow treatment of cells which have been removed from the patient, but do not allow treatment of cells remaining with the patient (human or animal).
The Nabel et al. article entitled “Site-Specific Gene Expression in Vivo by Direct Gene Transfer Into the Arterial Wall” in Science in 1990; 249(4974):1285-1288 discloses a technique for transfecting genes in vivo which has been used in the arteries of pigs. This technique uses a catheter with a dual balloon system at the tip of the catheter. The two balloons are inflated to create a temporary chamber which allows the exposure of the arterial wall to a viral transporting agent in solution. This has been used successfully to transfect the arterial wall with a DNA-plasmid having a viral carrier. However, this double balloon method requires 30 minutes to bathe the arterial wall with the DNA-plasmid to be effective. This is not feasible in certain applications such as in the coronary circulation. Moreover, the time required for such a technique to work may pose severe problems even at other locations within the arteries of an animal or human.
The Lim et al. article entitled “Direct In Vivo Gene Transfer Into the Coronary and Peripheral Vasculatures of the Intact Dog” appearing in Circulation, volume 83, no. Jun. 6, 1991, pages 2007-2011, discloses a technique where endothelial cells are removed from the test animal and then transfected prior to reintroduction into the animal. In addition to that in vitro technique, the article describes in vivo transfection of arteries of dogs using catheters placed in peripheral vessels of the dogs. Proximal and distal lumens of the vessels were occluded with removable ligatures. In somewhat similar fashion to the dual balloon system, a temporary chamber is established and a transfection solution is supplied into that temporary chamber within the vessels of the animal. The article describes allowing the transfection solution to remain in the vessel for one hour.
In the two above incorporated by reference applications, the present inventor has disclosed cell treatment (more specifically cell transfection) of a patient's cells in vivo by use of a laser catheter. No admission is made or intended that these prior applications of the present inventor are necessarily prior art to the present application. However, it is noted that the present inventor has discovered the use of various additional techniques for in vivo transfection of a patient's cells. As used herein, in vivo shall refer to treatment of a patient's cells without removing the cells from the patient. Thus, in vivo treatment involves treatment of cells within or on the patient.
OBJECTS AND SUMMARY OF THE INVENTION
Accordingly, it is a primary object of the present invention to provide a new and improved cell transfection apparatus and method.
A more specific object of the present invention is to provide for highly efficient cell transfection in vivo.
A further object of the present invention is to provide for transfection of cells in vivo relatively quickly (i.e., the cells in vivo need not be exposed for such long periods that lengthy disruptions, such as blocking of artery flow, are required).
The above and other objects which will become more apparent as the description proceeds are realized by an apparatus for cell transfection including an instrument with a housing having a wall with at least one hole therein. A heater is operatively connected to the instrument so as to apply heat to cells of a patient in vivo. A source of treatment agent including a DNA plasmid is operatively connected to the instrument so as to apply treatment agent to the heated cells by way of a treatment channel inside the instrument and extending to the hole. The treatment agent is operable to transfect the heated cells.
The heater, which may also be called a heating means, may be realized by various alternate constructions. In a first embodiment, the heater includes an optical fiber within the instrument for applying laser energy by way of the hole to heat the cells. In a second embodiment, the heater includes an optical fiber within the instrument for heating an opaque portion of the instrument such that the opaque portion in turn heats the cells. In a third embodiment, the heater is an RF source which heats the cells by application of radio frequency energy. In a fourth embodiment, the heater is a microwave source which heats the cells by application of microwave energy. In a fifth embodiment, the heater is an electrical heater mounted to the housing. In a sixth embodiment, the heater is chemical heating material adjacent the hole. In a seventh embodiment, the instrument has a distal portion adjacent the hole and a proximal portion remote from the hole and the heater is adjacent the proximal portion for heating the cells by heating treatment fluid remote from the distal portion. Other embodiments use infrared or ultrasound in order to heat patient cells.
Regardless of the heater arrangement, the instrument is preferably a catheter for insertion in a patient. The catheter further includes a flushing solution channel terminating in a flushing solution exit for applying flushing solution to a treatment site in a patient. The catheter includes a balloon mounted thereon and a balloon channel connected to the balloon for inflating the balloon, the balloon serving to occlude a body passage when the catheter is used for cell transfection.
The method of transfecting cells of a patient in vivo includes applying heat to the cells of the patient in vivo and providing a treatment agent including a DNA plasmid to the heated cells such that the heated cells are transfected. The application of heat is accomplished from one or more of the steps selected from the group including: application of laser energy to the cells, application of laser energy to heat an opaque portion of a part of an apparatus in thermal transfer position relative to the patient such that the apparatus in turn heats the cells, the application of radio frequency energy to the cells, application of microwave energy to the cells, electrically heating the cells, chemically heating the cells, heating-the cells by infrared energy, heating the cells by ultrasound energy, and heating the treatment agent prior to its insertion in the patient such that the treatment agent heats the cells.
Preferably, the method further includes inserting a catheter into the patient, the catheter having a treatment agent channel, and wherein the heat is applied by way of the catheter and the treatment agent is provided by way of the treatment agent channel.
In one technique according to the present invention, heat is applied using application of l
Feeney William L.
Peffley Michael
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