Abstract: The disclosure provides artificial nucleic acid introns configured for selective splicing in cells with aberrant RNA splicing activity, e.g., neoplastic cells. The artificial intron can comprise a 5? splice site, a canonical 3? splice site, at least one cryptic 3? splice site, a pyrimidine-rich domain, and at least one branchpoint. Also provided are constructs integrating the artificial introns with exons in a configuration that, when the artificial intron is spliced out by the aberrant RNA splicing factors, encode a functional protein. Also disclosed are methods that employ the disclosed platform of selective expression, including, targeted gene therapy methods (e.g., in cancers), diagnostics and imaging, and drug screening.

Abstract: The disclosure provides methods of enhancing susceptibility of neoplastic, transformed, and/or cancer cells (“cancer cells”) to immunotherapeutic agents. The methods comprise contacting the cancer cell with an agent that modulates RNA splicing. In some embodiments, the method further comprise contacting the cancer cell with the immunotherapeutic agent, such as an immune checkpoint inhibitor. The disclosure also provides compositions and/or methods for treating a subject with cancer. In some embodiments, the disclosure provides compositions and methods for combination therapy that comprises administering to a subject with cancer an effective amount of an agent that modulates RNA splicing and a therapeutically effective amount of an immunotherapeutic agent, such as an immune checkpoint inhibitor.

Abstract: The current disclosure relates to methods and compositions for increasing functional expression of BRD9 in a cell. The methods and compositions can be incorporated into methods for treating cancer through the administration of BRD9 activating therapies. Accordingly, aspects of the disclosure relate to compositions and methods for treating cancer, a pre-malignant disease, or a dysplastic disease in a subject. The method can comprise administering a BRD9 activating therapy to the subject.

Abstract: The present disclosure provides compositions and methods for treating cellular hyperproliferative disorders with a PHF5? inhibitor, such as siRNA, shRNA, antisense oligonucleotides, or pharmaceutical compounds. Exemplary cellular hyperproliferative disorders that can be treated with the PHF5? antagonists of the present disclosure include cancers, such as gliomas, adenocarcinomas, cervical cancer or prostate cancer.

Abstract: The present invention discloses the process of supplying high pressure (e.g., 30 atmospheres) CO that has been preheated (e.g., to about 1000° C.) and a catalyst precursor gas (e.g., Fe(CO)5) in CO that is kept below the catalyst precursor decomposition temperature to a mixing zone. In this mixing zone, the catalyst precursor is rapidly heated to a temperature that results in (1) precursor decomposition, (2) formation of active catalyst metal atom clusters of the appropriate size, and (3) favorable growth of SWNTs on the catalyst clusters. Preferably a catalyst cluster nucleation agency is employed to enable rapid reaction of the catalyst precursor gas to form many small, active catalyst particles instead of a few large, inactive ones. Such nucleation agencies can include auxiliary metal precursors that cluster more rapidly than the primary catalyst, or through provision of additional energy inputs (e.g., from a pulsed or CW laser) directed precisely at the region where cluster formation is desired.

Abstract: The present invention discloses the process of supplying high pressure (e.g., 30 atmospheres) CO that has been preheated (e.g., to about 1000° C.) and a catalyst precursor gas (e.g., Fe(CO)5) in CO that is kept below the catalyst precursor decomposition temperature to a mixing zone. In this mixing zone, the catalyst precursor is rapidly heated to a temperature that results in (1) precursor decomposition, (2) formation of active catalyst metal atom clusters of the appropriate size, and (3) favorable growth of SWNTs on the catalyst clusters. Preferably a catalyst cluster nucleation agency is employed to enable rapid reaction of the catalyst precursor gas to form many small, active catalyst particles instead of a few large, inactive ones. Such nucleation agencies can include auxiliary metal precursors that cluster more rapidly than the primary catalyst, or through provision of additional energy inputs (e.g., from a pulsed or CW laser) directed precisely at the region where cluster formation is desired.

Abstract: The present invention discloses the process of supplying high pressure (e.g., 30 atmospheres) CO that has been preheated (e.g., to about 1000° C.) and a catalyst precursor gas (e.g., Fe(CO)5) in CO that is kept below the catalyst precursor decomposition temperature to a mixing zone. In this mixing zone, the catalyst precursor is rapidly heated to a temperature that results in (1) precursor decomposition, (2) formation of active catalyst metal atom clusters of the appropriate size, and (3) favorable growth of SWNTs on the catalyst clusters. Preferably a catalyst cluster nucleation agency is employed to enable rapid reaction of the catalyst precursor gas to form many small, active catalyst particles instead of a few large, inactive ones. Such nucleation agencies can include auxiliary metal precursors that cluster more rapidly than the primary catalyst, or through provision of additional energy inputs (e.g., from a pulsed or CW laser) directed precisely at the region where cluster formation is desired.

Abstract: Metal Nanoshells having partial coverage of a substrate or core particle and methods of making them are provided. A method of making a partial metal nanoshell preferably includes asymmetrically confining a substrate particle and selectively layering a metallic material over the substrate particle according to the asymmetry. Confining the substrate particle may include attaching it to a support defining an exposed portion and a contact portion. The method may include either chemically modifying the substrate particle. The solid angle of coverage of the partial metal nanoshell may be influenced by the nature of the chemical modification, such as alternatives of activating and passivating the exposed portion.

Abstract: Metal Nanoshells having partial coverage of a substrate or core particle and methods of making them are provided. A method of making a partial metal nanoshell preferably includes asymmetrically confining a substrate particle and selectively layering a metallic material over the substrate particle according to the asymmetry. Confining the substrate particle may include attaching it to a support defining an exposed portion and a contact portion. The method may include either chemically modifying the substrate particle. The solid angle of coverage of the partial metal nanoshell may be influenced by the nature of the chemical modification, such as alternatives of activating and passivating the exposed portion.