Controlled surface-associated delivery of genes and oligonucleotides

A method for increasing transgene expression, comprising making a controlled nucleic acid delivery system, said system comprising forming nucleic acid polylinker complexes capable of being delivered to cells cultured on a support substrate, wherein said complexes are covalently or non-covalently immobilized to the surface of a support substrate, and wherein said method comprises:

• a) contacting a nucleic acid with a polylinker to form a nucleic acid-polylinker complex;
• b) immobilizing the nucleic acid-polylinker complex to a support substrate;
• and
• c) adding cells to the support substrate after immobilization of the nucleic acid-polylinker complex to the support substrate,
• wherein the release of nucleic acid from the nucleic acid-polylinker complexes is further enhanced when the support substrate containing the complexes is treated with serum or is incubated in conditioned medium.

A method for increasing transgene expression, comprising the steps of:

• a) making a controlled nucleic acid delivery system by contacting a nucleic acid with a polylinker to form a nucleic acid-polylinker complex, wherein said complex is formed prior to addition to a support substrate;
• b) immobilizing the nucleic acid-polylinker complex to a support substrate;
• wherein said immobilizing is accomplished by covalent or non-covalent means, and
• c) adding the cells into which transgene expression is desired to the support substrate after immobilization of the nucleic acid-polylinker complex to the support substrate.

A method for increasing transgene expression, wherein said method promotes transfection of primary cells, comprising the steps of:

• a) making a controlled nucleic acid delivery system by contacting a nucleic acid with a polylinker to form a nucleic acid-polylinker complex;
• b) immobilizing the nucleic acid-polylinker complex to a support substrate;
• wherein said immobilizing is accomplished by covalent or non-covalent means, and
• c) adding the cells into which transgene expression is desired to the support substrate after immobilization of the nucleic acid-polylinker complex to the support substrate, wherein the biodegradable material is a hydrogel and the non-biodegradable material is polystyrene or gold, and wherein the hvdrogel comprises a mixture of hyaluronic acid and collagen.

A method for increasing transgene expression, comprising the steps of:

• a) making a controlled nucleic acid delivery system by contacting a nucleic acid with a polylinker to form a nucleic acid-polylinker complex;
• b) immobilizing the nucleic acid-polylinker complex to a support substrate;
• wherein said immobilizing is accomplished by covalent or non-covalent means, and
• c) adding the cells into which transgene expression is desired to the support substrate after immobilization of the nucleic acid-polylinker complex to the support substrate,
• wherein said method further comprises release of the nucleic acid from the substrate, wherein the release is optimized by using conditioned medium.