Publication Date

2015-07-31

Availability

Embargoed

Embargo Period

2017-07-30

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Biochemistry and Molecular Biology (Medicine)

Date of Defense

2015-06-17

First Committee Member

Joaquin J. Jimenez

Second Committee Member

Thomas K. Harris

Third Committee Member

Eleonore Beurel

Fourth Committee Member

Robert Perez

Abstract

This proof of principle study explores dendrimer based technology in designing and implementing tissue-specific targeting dendrimers that can act as carriers of biologically active proteins in the treatment of disease. Here, we show a dendrimer based delivery system is effective in delivering a functionally active protein to a tissue-specific target, in this case skeletal muscle, and show in vivo therapeutic effects in the treatment of Type II Diabetes. Out of the many proteins involved in glycolysis within skeletal muscle cells whose mis-regulation can be observed in the diabetic disease state, we have selected one, PROTEIN A, for use in this proof-of-principle study. Here we describe the effectiveness of our dendrimer based system comprised of a Poly(amido amine) (PAMAM) generation 5 (G5) dendrimer and skeletal muscle targeting peptides (SMPTs), denoted as G5-SMTP, in delivering PROTEIN A to skeletal muscle. The cumulative data presented here demonstrates that G5-SMTP can successfully be used as a platform for skeletal muscle targeted delivery of the functionally active protein, PROTEIN A, to produce therapeutic effects in diabetic murine models.

Keywords

Dendrimer; Diabetes; Skeletal Muscle Targeting Peptide

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