Gregory S Hunter

US Patent:

20070218465, Sep 20, 2007

Filed:

Jun 29, 2006

Appl. No.:

11/427604

Inventors:

Gregory A. Hunter - Tampa FL, US
Gloria C. Ferreira - Tampa FL, US

Assignee:

UNIVERSITY OF SOUTH FLORIDA - Tampa FL

International Classification:

C40B 30/06
C40B 40/08
A61K 31/409
A61K 31/195

US Classification:

435 6, 435 912, 514410, 514561

Abstract:

Systems and methods for increasing protoporphyrin IX accumulation in a target cell population using aminolevulinate synthase variants. Aminolevulinic acid-mediated photodynamic therapy is a promising approach to treating dysplasic disorders such as cancer and atherosclerosis, but is limited by the lack of a means to deliver optimal quantities of aminolevulinic acid selectively to the target cells, and thereby ensure the best therapeutic response. The disclosed invention provides a means for enhancing the natural production of aminolevulinic acid selectively within target cells to levels predetermined to give an optimal therapeutic response, and is expected to lead to increased efficacy of treatment, possibly broadening the scope of diseases treatable by photodynamic therapy considerably. The disclosed invention is also amenable to patient specific therapy, meaning that a patient's target cells could be used to screen for the aminolevulinic acid delivery system most appropriate for the patient's needs.

US Patent:

20100248328, Sep 30, 2010

Filed:

Jan 21, 2010

Appl. No.:

12/691359

Inventors:

Gregory A. Hunter - Tampa FL, US
Gloria C. Ferreira - Tampa FL, US
Thomas Lendrihas - Temple Terrace FL, US

Assignee:

UNIVERSITY OF SOUTH FLORIDA - TAMPA FL

International Classification:

C12N 9/10

US Classification:

435193

Abstract:

The rate of porphyrin biosynthesis in mammals is controlled by the activity of the pyridoxal 5′-phosphate-dependent enzyme 5-aminolevulinate synthase. Assuming the turnover in this enzyme is controlled by conformational dynamics at a highly conserved active site loop, a variant library was constructed by targeting imperfectly conserved non-catalytic loop residues and the effects on product and porphyrin production were examined. Functional loop variants of the enzyme were tested for porphyrin fluorescence, which varied widely and thus facilitated identification of clones encoding unusually active enzyme variants. Nine loop variants leading to high in vivo porphyrin production were purified and characterized kinetically. Steady-state catalytic efficiencies for the two substrates were increased by up to one hundred-fold. The data support the postulate that the active site loop controls the rate of product and porphyrin production in vivo and suggest the possibility of an as yet undiscovered means of allosteric regulation.