Peg-prom mediated surface expression of avidin/streptavidin
AssigneesThe Johns Hopkins University, Virginia Commonwealth University
InventorsPaul B. FISHER, Swadesh K. Das, Mitchell E. MENEZES, Devanand Sarkar, Martin G. POMPER
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Abstract
The presently disclosed subject matter relates to compositions and methods directed to cancer theranostic nucleic acid constructs that permit simultaneous cancer-specific viral replication, expression of a diagnostic gene product, and expression of a therapeutic gene.
Claims45
A nucleic acid construct comprising a first promoter operably linked to a gene encoding avidin or streptavidin, and a second promoter operably linked to a gene encoding a therapeutic agent, wherein the first promoter is cancer-selective.
The nucleic acid construct of claim 8, wherein the immunomodulatory cytokine is mda-7/IL-24.
A method of imaging and treating cancerous cells in a subject, comprising the steps of:
- a. administering to the subject a nucleic acid construct comprising a first promoter operably linked to a gene encoding avidin or streptavidin, and a second promoter operably linked to a gene encoding a therapeutic agent, wherein the first promoter is cancer-selective;
- b. contacting the avidin or streptavidin with a biotinylated adduct comprising an imaging agent;
- and
- c. detecting a detectable signal from the imaging agent;
- wherein the gene encoding the therapeutic agent is expressed in the cancerous cells.
A method of treating cancerous cells in a subject, comprising the steps of:
- a. administering to the subject a nucleic acid construct comprising a first promoter operably linked to a gene encoding avidin or streptavidin, and a second promoter operably linked to a gene encoding a first therapeutic agent, wherein the first promoter is cancer-selective and wherein the gene encoding the therapeutic agent is expressed in the cancerous cells;
- and
- b. contacting the avidin or streptavidin with a biotinylated adduct comprising a second therapeutic agent.
A composition comprising an ultrasound targeted microbubble population, wherein the microbubble population stably binds a nucleic acid construct comprising a first promoter operably linked to a gene encoding avidin or streptavidin, and a second promoter operably linked to a gene encoding a therapeutic agent, wherein the first promoter is cancer-selective.
A method for delivering a nucleic acid construct to cancerous cells in a subject, comprising the steps of:
- a. providing an ultrasound targeted microbubble population stably binding the nucleic acid construct;
- b. providing an ultrasound device capable of directing the microbubble population to the cancer cells;
- c. directing the microbubble population to the cancer cells with the ultrasound device;
- and
- d. bursting the microbubble population under conditions such that the nucleic acid construct is delivered to the cancer cells;
- wherein the nucleic acid construct comprises a first promoter operably linked to a gene encoding avidin or streptavidin, and a second promoter operably linked to a gene encoding a therapeutic agent, wherein the first promoter is cancer-selective.
Dependencies are inferred from the claim text.