In vivo gene transfer for wound healing

Abstract

The present invention relates to an in vivo method for specific targeting and transfer of DNA into mammalian repair cells. The transferred DNA may include any DNA encoding a therapeutic protein of interest. The invention is based on the discovery that mammalian repair cells proliferate and migrate into a wound site where they actively take up and express DNA. The invention further relates to pharmaceutical compositions that may be used in the practice of the invention to transfer the DNA of interest. Such compositions include any suitable matrix in combination with the DNA of interest.

Description

[0001] This application is a divisional application. The filing date of the original application is April 11, 1997, the application number is 97195326.0 (PCT / US97 / 07301), and the title of the invention is "in vivo gene transfer for wound healing". [0002] 1. introduce [0003] The present invention relates to novel in vivo methods for the presentation and direct transfer of DNA encoding a therapeutic protein of interest into mammalian repair cells. The method involves implanting a matrix containing the DNA of interest (herein referred to as "gene activation matrix") into a fresh wound site. Repair cells normally originating in the living tissue around the wound proliferate and migrate into the gene-activating matrix where they encounter the DNA, take it up and express it. The transfected repair cells thus serve as in situ bioreactors (located in the wound site), producing drugs (DNA encoded RNA, proteins, etc.) that heal the wound. [0004] The invention also relates to phar...

AI Technical Summary

Problems solved by technology

First, purification and / or recombinant production of therapeutic proteins is often an expensive and time-consuming process

Despite best efforts, purified protein preparations are often unstable, making storage and use cumbersome, and protein instability can lead to unintended inflammatory responses that are toxic to the host (for proteolytic breakdown products)

[0008] Second, systemic delivery of therapeutic proteins (i.e., cytokines) may be associated with severe adverse side effects in uninjured tissue

Due to proteolytic degradation, the protein has a short half-life in the body and the protein must also be administered repeatedly, which can lead to an immune response to the therapeutic protein

Circulation of therapeutic proteins in high doses is often toxic due to pleiotropic effects of the administered protein and can produce serious side effects

[0009] Third, the efficiency of exogenous delivery of recombinant proteins is low

Although viral vectors are highly efficient for gene transfer, major disadvantages associated with their use include the inability of many viral vectors to infect non-dividing cells; problems related to insertional mutagenesis; inflammatory responses to the virus and potential helper virus production, and / or production and transmission of harmful viruses to other human patients

[0016] In addition to the inefficient uptake and expression of exogenous DNA by most cell types, many target cell populations have been found to be in such low numbers in the body that the efficiency of DNA presentation to specific target cell types is even further reduced

Currently, there are no protocols or methods for increasing the efficiency of directing DNA to target cell populations

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