Methods and systems for improved nucleic acid delivery via ultrasound

A method for expressing a nucleic acid in a target cell of a subject, the method comprising administering to the subject the nucleic acid, wherein the nucleic acid comprises a cargo polynucleotide and a nuclear localization element, wherein the nuclear localization element increases expression of the cargo polynucleotide in the target cell by at least 1.25 fold as compared to a nucleic acid lacking the nuclear localization element.

5-6. (canceled)

(canceled)

(canceled)

14-23. (canceled)

25-26. (canceled)

34-79. (canceled)

84-120. (canceled)

A pharmaceutical composition comprising:

• a. a microbubble;
• and
• b. a nucleic acid comprising (1) a cargo polynucleotide comprising an expression cassette that comprises a therapeutic transgene and (2) an aptamer, wherein the aptamer comprises a sequence configured to increase nuclear localization.

122-248. (canceled)

An isolated nucleic acid comprising:

• a cargo polynucleotide comprising an expression cassette that encodes a therapeutic transgene configured for expression in a target cell of a subject, and a nuclear localization element configured to increase expression of the cargo polynucleotide in the target cell.

250-297. (canceled)