Tripartite cancer theranostic nucleic acid constructs
AssigneesVirginia Commonwealth University, The Johns Hopkins 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 generally relates to genetic constructs and methods for their use in cancer imaging, cancer treatment, and combined imaging and treatment protocols. In particular, the presently disclosed subject matter relates to tripartite cancer theranostic nucleic acid constructs that permit simultaneous cancer specific viral replication, expression of a diagnostic gene product, and expression of a therapeutic gene.
Claims37
A tripartite nucleic acid construct comprising a first promoter operably linked to at least one gene required for viral replication, a second promoter operably linked to a gene encoding an imaging agent, and a third promoter operably linked to a gene encoding a therapeutic agent, wherein the first promoter and the second promoter are each cancer-selective.
A method of imaging and treating cancerous cells in a subject, comprising the steps of:
- a. administering to the subject a tripartite nucleic acid construct comprising a first promoter operably linked to at least one gene required for viral replication, a second promoter operably linked to a gene encoding an imaging agent, and a third promoter operably linked to a gene encoding a therapeutic agent, wherein the first promoter and the second promoter are each cancer-selective;
- and
- b. imaging cancerous cells in the subject by detecting a detectable signal from the imaging agent, wherein the gene encoding the therapeutic agent is expressed in the cancerous cells.
A composition comprising an ultrasound targeted microbubble population, wherein the microbubble population stably binds a tripartite nucleic acid construct, and wherein the tripartite nucleic acid construct comprises a first promoter operably linked to at least one gene required for viral replication, a second promoter operably linked to a gene encoding an imaging agent, and a third promoter operably linked to a gene encoding a therapeutic agent, wherein the first promoter and the second promoter are each cancer-selective.
A method for delivering a tripartite nucleic acid construct to cancerous cells in a subject, comprising the steps of:
- a. providing an ultrasound targeted microbubble population stably binding the tripartite 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 tripartite nucleic acid construct is delivered to the cancer cells;
- wherein the tripartite nucleic acid construct comprises a first promoter operably linked to at least one gene required for viral replication, a second promoter operably linked to a gene encoding an imaging agent, and a third promoter operably linked to a gene encoding a therapeutic agent, wherein the first promoter and the second promoter are each cancer-selective.
Dependencies are inferred from the claim text.