Electrical field therapy with reduced histopathological change in muscle
First Claim
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1. A method for delivering a therapeutic agent to a subject, comprising;
- introducing an effective amount of at least one therapeutic agent into a target muscle tissue site of a subject, wherein the therapeutic agent comprises a polynucleotide that encodes a therapeutic protein or peptide; and
generating an electric field at the target muscle tissue site by introducing from 1 to about 4 monopolar DC pulses, each pulse having a duration of about 10 ms to about 100 ms, to generate a nominal field strength of about 100 V/cm to about 300 V/cm at the target muscle tissue site.
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Abstract
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.
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Citations
36 Claims
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1. A method for delivering a therapeutic agent to a subject, comprising;
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introducing an effective amount of at least one therapeutic agent into a target muscle tissue site of a subject, wherein the therapeutic agent comprises a polynucleotide that encodes a therapeutic protein or peptide; and generating an electric field at the target muscle tissue site by introducing from 1 to about 4 monopolar DC pulses, each pulse having a duration of about 10 ms to about 100 ms, to generate a nominal field strength of about 100 V/cm to about 300 V/cm at the target muscle tissue site. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12)
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13. An in viva method for expressing a therapeutic polypeptide or peptide encoded by an isolated polynucleotide delivered into cells in a subject, comprising;
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a) introducing at least one isolated polynucleotide encoding a therapeutic polypeptide or peptide into a target muscle tissue site of a subject; and b) generating an electric field a the target muscle tissue site by introducing from 1 to about 4 monopolar DC pulses, each having a pulse duration of about 10 to about 100 ms, to generate a nominal field strength of about 100 V/cm to about 300 V/cm at the target muscle tissue site. - View Dependent Claims (14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34)
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35. A method for delivering a polynucleotide encoding a peptide or polypeptide to a target muscle tissue site, comprising:
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a) introducing an effective amount of at least one isolated polynucleotide encoding a peptide or polypeptide into a target muscle tissue site of a subject; b) introducing at least a conductive portion of an electrode needle array into the target muscle tissue; and c) applying from 1 to about 4 monopolar DC pulses having a duration of about 10 ins to about 100 ms each to generate a nominal field strength of about 100 V/cm to about 300 V/cm at the target muscle site, thereby delivering the polynucleotide to the target muscle tissue site. - View Dependent Claims (36)
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Specification