Expression of exogenous polynucleotide sequences in a vertebrate

A method for delivering a pharmaceutical or immunogenic polypeptide to the interior of a cell of a vertebrate in vivo, comprising the step of:

• introducing a preparation comprising a pharmaceutically acceptable injectable carrier and a naked polynucleotide operatively coding for said polypeptide into the interstitial space of a tissue comprising said cell, whereby said naked polynucleotide is taken up into the interior of said cell and has an immunogenic or pharmacological effect on said vertebrate.

A method for treating a disease associated with the deficiency or absence of a specific polypeptide in a vertebrate, comprising the step of:

• introducing an injectable preparation comprising a pharmaceutically acceptable carrier and containing a naked polynucleotide operatively coding for said polypeptide into a vertebrate and permitting said polynucleotide to be incorporated into a cell, wherein said polypeptide is formed as the translation product of said polynucleotide and said deficiency or absence of said polypeptide is effectively treated.

A method for immunizing a vertebrate, comprising the step of:

• introducing an injectable preparation comprising a pharmaceutically acceptable carrier and a naked, expressible polynucleotide operatively coding for an immunogenic peptide interstitially into tissue of a vertebrate whereby an immunogenic translation product of said polynucleotide is formed by a cell of said tissue, thereby eliciting an immune response against said immunogen.

A method for introducing a polynucleotide into muscle cells in vivo, comprising the steps of:

• providing a composition comprising a naked polynucleotide in a pharmaceutically acceptable carrier;
• and
• contacting said composition with muscle tissue of a vertebrate in vivo, whereby said polynucleotide is introduced into muscle cells of said tissue.

A method for obtaining long term administration of a polypeptide to a vertebrate, comprising the step of introducing a naked DNA sequence operatively coding for said polypeptide interstitially into tissue of said vertebrate, whereby cells of said tissue produce said polypeptide for at least 3 months.

A method for obtaining transitory expression of a polypeptide in a vertebrate, comprising the step of introducing a naked mRNA sequence operatively coding for said polypeptide interstitially into tissue of said vertebrate, whereby cells of said tissue produce said polypeptide for less than about 10 days.

A method for treatment of muscular dystrophy, comprising the steps of:

• introducing a therapeutic amount of a composition comprising a polynucleotide operatively coding for dystrophin in a pharmaceutically acceptable carrier in vivo into muscle tissue of an animal suffering from muscular dystrophy, whereby said polynucleotide is taken up into cells of said tissue and dystrophin is produced in vivo.

A pharmaceutical product, comprising:

• naked antisense polynucleotide in physiologically acceptable administrable form, in a container;
• and
• a notice associated with said container in form prescribed by a governmental agency regulating the manufacture, use, or sale of pharmaceuticals, which notice is reflective of approval by said agency of said form of said polynucleotide for human or veterinary administration.

Use of naked polynucleotide operatively coding for a physiologically active polypeptide in the preparation of a pharmaceutical for introduction interstitially into tissue to cause cells comprising said tissue to produce said polypeptide.

Use of naked antisense polynucleotide in the preparation of a pharmaceutical for introduction interstitially into tissue of a vertebrate to inhibit translation of polynucleotide in cells of said vertebrate.