In Vivo Gene Therapy Delivery Procedure and Device

Patent metadata

Field	Value
Publication number	US-2021146127-A1
Application number	US-202117160832-A
Country	US
Kind code	A1
Filing date	Jan 28, 2021
Priority date	Jul 24, 2018
Publication date	May 20, 2021
Grant date	—

Abstract

A “localizable” systemic gene therapy system is provided substantially increasing the transfection efficiency of the gene vectors into targeted tissue cells and substantially reducing the escape of the gene vectors from the targeted tissue volume, such as would waste the vectors, promote undesired immune reactions, and/or incur prohibitive costs for the required dose of gene-containing virus vectors. In this regard, the invention provides a means to simultaneously achieve local electroporation and gene-containing vector injection in a portion of a vascularized organ. It includes two double-balloon catheters that create contained volumes in parallel blood vessels for the introduction of vectors with reduced loss along with electrodes providing electroporation of the cells in the same location where the vectors are injected.

First claim

What we claim is:

1 . A gene therapy delivery system comprising:
a first balloon catheter providing a distal end having a first and second inflatable balloon spaced apart along the distal end to define an intervening catheter section and at least one passageway through a delivery lumen of the intervening catheter section for the delivery of a gene vector; a second balloon catheter providing a distal end having a first and second inflatable balloon spaced apart along the distal end to define an intervening catheter section and at least one passageway through a delivery lumen of the intervening catheter section for the delivery of a gene vector; a first electrode extending along the first balloon catheter; a second electrode extending along the second balloon catheter; and a power supply providing a voltage across the first and second balloon catheters.

2 . The system of claim 1 wherein the first and second electrode extend within the delivery lumen of the first and second balloon catheter, respectively.

3 . The system of claim 1 wherein the first and second electrode terminate before a distal tip of the first and second balloon catheters, respectively.

4 . The system of claim 1 wherein the first and second electrode extend substantially parallel with a catheter sidewall.

5 . The system of claim 1 wherein the first and second electrode provides a coaxial conductor having an inner and an outer coaxial conductive element and wherein the outer conductive element is removed from the coaxial conductor within the intervening catheter section to allow transmission of electrical field for electroporation.

6 . The system of claim 5 wherein a proximal end of the catheter provides an electrical connector providing separate connections to the inner and outer coaxial conductive elements.

7 . The system of claim 5 wherein the inner conductive element is stainless steel.

8 . The system of claim 5 wherein the first and second electrode provides a coaxial conductor wherein the coaxial conductor is insulated within the intervening catheter section to prevent current flow to an exterior of the first and second balloon catheters.

9 . The system of claim 1 wherein the intervening catheter section includes a plurality of perfusion holes spaced along the intervening catheter section.

10 . The system of claim 1 wherein the intervening catheter section includes at least one perfusion hole centered within the intervening catheter section.

11 . The system of claim 1 wherein one of the first and second inflatable balloon is positioned at a distal tip of the first and second balloon catheters.

12 . The system of claim 1 wherein the catheter has at least two lumens, one communicating with at least one of the balloon catheters and the other communicating with the delivery lumen.

13 . A method of gene therapy comprising:
providing a first balloon catheter providing a distal end having a first and second inflatable balloon spaced apart along the distal end to define an intervening catheter section and at least one passageway through a delivery lumen of the intervening catheter section for the delivery of a gene vector, a first electrode extending along the first balloon catheter; providing a second balloon catheter providing a distal end having a first and second inflatable balloon spaced apart along the distal end to define an intervening catheter section and at least one passageway through a delivery lumen of the intervening catheter section for the delivery of a gene vector, a second electrode extending along the second balloon catheter; inserting the first balloon catheter into a first blood vessel of a patient; inserting the second balloon catheter into a second blood vessel of the patient; injecting a gene vector through the delivery lumen of the intervening catheter section to deliver the gene vector into surrounding cells; and delivering an electrical charge to one of the first and second electrodes to produce a voltage across between the first and second balloon catheter.

14 . The method of claim 13 wherein the first and second electrical conductor electrodes are separated by an average distance of 5-30 mm.

15 . The method of claim 13 wherein one of the first and second electrodes receives the electrical charge and the other is a return electrode.

Assignees

• Wisconsin Alumni Res Found

Inventors

• Hagness Susan
• Aiken Erik
• Booske John
• Sollinger Hans
• Laeseke Paul
• Alam Tausif

Classifications

• A61N1/325 Primary

  for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body (electrodes for external use A61N1/0428) · CPC title

• A61M25/10

  Balloon catheters ({A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02;} inflatable balloons for placing stents or stent-grafts A61F2/958 {; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00}) · CPC title

• A61N1/327 Primary

  for enhancing the absorption properties of tissue, e.g. by electroporation · CPC title

• A61M31/00

  Devices for introducing or retaining media, e.g. remedies, in cavities of the body (A61M25/00 takes precedence {; introducing or retaining ophthalmic products into the ocular cavities A61F9/0008}) · CPC title

• A61M2025/1052

  for temporarily occluding a vessel for isolating a sector · CPC title