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Full-Text Articles in Life Sciences

Design And Delivery Of Synthetic Mrna By A Peptide Nanoparticle, John H. Lockhart Oct 2019

Design And Delivery Of Synthetic Mrna By A Peptide Nanoparticle, John H. Lockhart

USF Tampa Graduate Theses and Dissertations

The field of synthetic mRNA therapeutics is a rapidly expanding arm of gene therapies. The use of mRNA provides multiple benefits over viral or DNA vectors. synthetic mRNA vectors are immediately translated into protein after entering the cytoplasm of cells in contrast to DNA vectors that must first be transcribed to mRNA in the nucleus. This allows synthetic mRNA to produce a therapeutic protein in any cell type, including non-dividing cells. In addition, the non-replicative nature of mRNA means that insertional mutagenesis or generation of escape mutants is not a concern. However, the stimulation of innate immune responses by unmodified …


Assessing The Structure-Function Relationships Of The Apolipoprotein(A) Kringle Iv Sub-Type 10 Domain, Matthew J. Borrelli Aug 2019

Assessing The Structure-Function Relationships Of The Apolipoprotein(A) Kringle Iv Sub-Type 10 Domain, Matthew J. Borrelli

Electronic Thesis and Dissertation Repository

Elevated plasma lipoprotein(a) (Lp(a)) is the most prevalent heritable risk factor in the development of cardiovascular disease. The apolipoprotein(a) (apo(a)) component of Lp(a) is strongly implicated in the pathogenicity of Lp(a). It is hypothesized that the inflammatory potential of Lp(a)/apo(a) is mediated by the lysine binding ability of the apo(a) kringle IV10 (KIV10) domain, along with its covalently bound oxidized phospholipid (oxPL). Using targeted mutagenesis, two novel null alleles for the LPA gene that generate non-secretable apo(a) species have been identified, resulting from amino acid substitutions in the KIV10 domain. A potential mechanism by which KIV10 oxPL modification is enriched …