Abstract: Disclosed herein is a system that addresses the current challenges described by combining three existing technologies and an improved nuclear RNA delivery system to generate a first-in-class cellular therapy that can secrete a cancer specific suicide gene for the treatment of several cancers. The system generally involves a first poly nucleotide encoding retroviral elements that preferentially binds and facilitates formation and secretion of vesicles carrying its own RNA messenger operably linked to a first expression control sequence; a second polynucleotide encoding an RNA therapeutic having a nuclear retention sequence that is flanked by packaging signals for the retroviral elements operably linked to a second expression control sequence; and a third polynucleotide encoding a membrane fusion protein operably linked to a third expression control sequence.

Abstract: As disclosed herein, the long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed and prognostic in Chronic Myelomonocytic Leukemia (CMML). MALAT1 depletion is disclosed herein as therapeutic strategy for treating CMML and other MALAT1 overexpressing leukemias. Also disclosed herein is a method of treating a subject with a leukemia that involves co-administering to the subject a MALAT1 silencing agent and a therapeutically effective amount of a differentiation agent, such as all-trans retinoic acid (ATRA).

Abstract: Methods, systems, and apparatus, including computer programs encoded on a computer storage medium, including a system for providing treatment suggestions. The system includes a data warehouse including patient data for a plurality of patients associated with one or more care facilities, and one or more processors including instructions for implementing an evidence-based clinical decision engine. The engine is operable to: identify patient cohorts defined by the data in the data warehouse including identifying relevant cohorts that include a population of patients who are similar, both by phenotype and genotype, to a candidate patient; evaluate the patient cohorts to identify a cohort that is a best match for the candidate patient based on historical treatment information for patients in each candidate patient cohort; select a cohort from the plurality of cohorts; and provide a treatment suggestion to the patient or a care provider based on the selection.