# US 6,794,369 B2 · Methods, systems, and kits for intravascular nucleic acid delivery > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 6,794,369 B2 - Document ID: US6794369B2 - Status: Granted - Kind: B2 - Application number: 10/216,061 - Filed: 2002-08-09 - Published: 2003-02-27 - Granted: 2004-09-21 - Earliest claimed: 1997-12-31 - Assignees: Pharmasonics, Inc. - Inventors: Christopher M. H. Newman; Axel F. Brisken - Web page: https://patentgrep.com/patent/US6794369B2 ## CPC - A61N 1/325: {for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body (electrodes for external use A61N1/0428)} - A61M 37/0092: {using ultrasonic, sonic or infrasonic vibrations, e.g. phonophoresis} - A61B 17/2202: {the ultrasound transducer being inside patient's body at the distal end of the catheter} - A61B 2017/22082: {after introduction of a substance} - A61M 2025/105: {having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes} - A61M 2210/12: Blood circulatory system - A61N 1/306: {Arrangements where at least part of the apparatus is introduced into the body} - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) - A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)} - A61B: DIAGNOSIS; SURGERY; IDENTIFICATION (usefulness limited to only animals A61D) ## Abstract Nucleic acid transfection of vascular smooth muscle cells is enhanced by the application of vibrational energy to the cells. By applying vibrational energy at frequency in the range from 1 kHz to 10 MHz and at an intensity in the range from 0.01 W/cm2 to 100 W/cm2, significant enhancement of the uptake of nucleic acids into vascular smooth muscle cells can be achieved. ## Claims ### Claim 1 A method for intravascular nucleic acid delivery, said method comprising: providing a flexible catheter having a vibrational transducer disposed near its distal end; intravascularly positioning the distal end of the catheter at a target region within a blood vessel; delivering nucleic acids to vascular smooth muscle cells which line a wall of the blood vessel; and energizing the transducer to deliver vibrational energy to the wall at a frequency and intensity selected to enhance uptake of the nucleic acids by the smooth muscle cells, wherein expression of the nucleic acids in the cells exposed to the vibrational energy is at least two-fold greater than in comparable cells not exposed to vibrational energy. ### Claim 2 (depends on 1) A method as in claim 1, wherein the expression of the nucleic acids is at least four-fold greater than in comparable cells not exposed to vibrational energy. ### Claim 3 (depends on 1) A method as in claim 1, wherein the vibratory energy is at a frequency in the range from 1 kHz to 10 MHz. ### Claim 4 (depends on 3) A method as in claim 3, wherein the vibratory energy has an intensity in the range from 0.01 W/cm2 to 100 W/cm2. ### Claim 5 (depends on 4) A method as in claim 4, wherein the vibratory energy is delivered with a duty cycle in the range from 1% to 100%. ### Claim 6 (depends on 5) A method as in claim 5, wherein the vibratory energy is applied for a cumulative treatment time in the range from 10 seconds to 900 seconds. ### Claim 7 (depends on 1) A method as in claim 1, wherein the interface surface directly contacts the blood vessel wall within the target region. ### Claim 8 (depends on 1) A method as in claim 1, wherein the interface surface is spaced-apart from the blood vessel wall, wherein ultrasonic energy is transmitted through a liquid medium containing the nucleic acids disposed between the interface surface and the wall. ### Claim 9 (depends on 1) A method as in claim 1, wherein the vibrational exciting step comprises vibrating the surface in a radial direction. ### Claim 10 (depends on 1) A method as in claim 1, wherein the vibrational exciting step comprises vibrating the surface in an axial direction. ### Claim 11 (depends on 1) A method as in claim 1, further comprising expanding a pair of axially spaced-apart balloons disposed on either side of the vibrational surface to localize a solution containing the nucleic acids as the surface is vibrated. ### Claim 12 (depends on 1) A method as in claim 1, wherein the nucleic acids are delivered through the flexible catheter. ### Claim 13 (depends on 1) A method as in claim 1, wherein the nucleic acids are selected from the group consisting of genes, gene fragments, sense polynucleotides, anti-sense polynucleotides, and oligonucleotides. ### Claim 14 (depends on 13) A method as in claim 13, wherein the nucleic acids encode an angiogenic factor eNOS, TIMP, or p21. ### Claim 15 (depends on 1) A method as in claim 1, wherein the nucleic acids are delivered after the target region has been treated to enlarge or remove an occlusion. ### Claim 16 (depends on 15) A method as in claim 15, wherein the prior treatment is selected from the group consisting of angioplasty, atherectomy, and stenting. ### Claim 17 A system comprising: a catheter having a vibratory interface surface; and a nucleic acid reagent which can be intravascularly delivered by the catheter.