Methods of downregulating CCL20 genes for treatment of traumatic brain injuries

A method of enhancing efficacy of human mesenchymal stem cells (hMSCs) to treat a traumatic brain injury (TBI) by prior gene silencing in a patient in need thereof, comprising:

• administering at least two PAMAM/DNA dendriplexes to the patient in need thereof at least once, each of the at least two PAMAM/DNA dendriplexes consisting of:
• at least one modified polyamidoamine (PAMAM) dendrimer nanoparticle modified by using extrusion to remove large particles to obtain a size of about 5 nm with 0.150 polydispersity index;
• and
• at least one short hairpin RNA (shRNA)-encoding DNA plasmid complexed via electrostatic interactions to an outer surface of the at least one modified PAMAM dendrimer nanoparticle by vigorous vortexing;
• wherein the at least one plasmid DNA and the at least one modified PAMAM dendrimer are complexed at a final nitrogen to phosphate (N/P) ratio of 10;
• and
• subsequently administering a therapeutically effective amount of hMSCs to the patient in need thereof;
• wherein the at least one shRNA-encoding DNA plasmid comprises a nucleotide sequence encoding at least one shRNA targeting chemokine ligand 20 (CCL20) and at least one shRNA targeting chemokine receptor 6 (CCR6).

A method of synergistically increasing brain derived neurotrophic factor (BDNF) in a patient following traumatic brain injury (TBI) comprising:

• administering at least once to the patient at least two PAMAM/DNA dendriplexes, each of the at least two PAMAM/DNA dendriplexes consisting of:
• at least one modified polyamidoamine (PAMAM) dendrimer nanoparticle modified by using extrusion to remove large particles to obtain a size of about 5 nm with 0.150 polydispersity index;
• and
• at least one short hairpin RNA (shRNA)-encoding DNA plasmid complexed via electrostatic interactions to an outer surface of the at least one modified PAMAM dendrimer nanoparticle by vigorous vortexing;
• wherein the at least one plasmid DNA and the at least one modified PAMAM are complexed at a final nitrogen to phosphate (N/P) ratio of 10;
• subsequently administering a therapeutically effective amount of human mesenchymal stem cells (hMSCs) to the patient;
• wherein the at least one shRNA-encoding DNA plasmid comprises a nucleotide sequence encoding at least one shRNA targeting chemokine ligand 20 (CCL20) and at least one shRNA targeting chemokine receptor 6 (CCR6);
• wherein at least one dendriplex is administered intranasally and at least one dendriplex is administered intravenously.