RNA interference (RNAi), a biological process for modulating gene expression using short interfering RNA (siRNA) molecules, has emerged as one of the most promising technologies for treating a wide range of difficult-to-cure diseases, including liver diseases, cancer, neurodegenerative diseases, etc. However, lack of effective means to deliver siRNA into targeted organs in the human body significantly hinders clinical applications of RNAi technology, particularly in liver therapy. Our proposal is specifically designed to address this critical challenge. Phase I work will focus on development of a patent-pending targeted siRNA delivery technology with real-time optimization capability. Applying the technology, we will optimize siRNA delivery to ex vivo liver tissue and demonstrate its clinical relevance by delivering specific siRNA to functionally knockdown certain therapeutic targets of liver diseases. Successful Phase I development will lead to extensive future animal study to demonstrate the utility of this novel siRNA delivery technology in controlling liver diseases, such as liver cirrhosis and alcoholic liver, which could potentially benefit millions of patients suffering from these formidable liver diseases.
Public Health Relevance: Success in this project will accelerate the progress of transferring advanced siRNA based therapeutic technology into clinical application. It will benefit public health by revolutionizing clinical treatment of a broad range of difficult-to-cure diseases such as cancers, liver diseases, viral infection, and cardiovascular diseases, etc.
Public Health Relevance Statement: Success in this project will accelerate the progress of transferring advanced siRNA based therapeutic technology into clinical application. It will benefit public health by revolutionizing clinical treatment of a broad range of difficult-to-cure diseases such as cancers, liver diseases, viral infection, and cardiovascular diseases, etc.
Project Terms: Address; Alcoholic; Alcoholic Cirrhosis; Alcoholic Liver Cirrhosis; Algorithms; Animal Disease Models; Animals; Biological; Biological Function; Biological Process; Body Tissues; Boozer; Cancer Genes; Cancer-Promoting Gene; Cancers; Cardiovascular Diseases; Cell Membrane Permeability; Cells; Cellular injury; Clinical Treatment; Clinical Trials, Phase I; Degenerative Diseases, Nervous System; Degenerative Neurologic Disorders; Dependent drinker; Development; Diagnosis, Ultrasound; Disease; Disorder; Early-Stage Clinical Trials; Echography; Echotomography; Effectiveness; Electrical Impedance; Exposure to; Feedback; Future; Gene Expression; Gene Products, RNA; Goals; Harvest; Hepatic Cirrhosis, Alcoholic; Hepatic Disorder; Human Figure; Human body; Image; Impedance; Investigation; Lead; Legal patent; Liver; Liver Cirrhosis, Alcoholic; Liver diseases; Liver neoplasms; Malignant Neoplasms; Malignant Tumor; Mammals, Mice; Measurement; Measures; Medical Imaging, Ultrasound; Messenger RNA; Methods and Techniques; Methods, Other; Mice; Monitor; Murine; Mus; Neoplasms, Hepatic; Neurodegenerative Diseases; Neurodegenerative Disorders; Neurologic Degenerative Conditions; Neurologic Diseases, Degenerative; Oncogenes; Organ; Patents; Patients; Pb element; Phase; Phase 1 Clinical Trials; Phase I Clinical Trials; Phase I Study; Portal Cirrhosis; Post-Transcriptional Gene Silencing; Post-Transcriptional Gene Silencings; Posttranscriptional Gene Silencing; Posttranscriptional Gene Silencings; Public Health; Quantitative RTPCR; Quantitative Reverse Transcriptase PCR; Quelling; RNA; RNA Interference; RNA Silencing; RNA Silencings; RNA, Messenger; RNA, Non-Polyadenylated; RNAi; Ribonucleic Acid; Sampling; Sequence-Specific Posttranscriptional Gene Silencing; Slice; Staging; System; System, LOINC Axis 4; Techniques; Technology; Therapeutic; Therapeutic Effect; Time; Tissues; Transforming Genes; Ultrasonic Imaging; Ultrasonogram; Ultrasonography; Ultrasound Test; Ultrasound, Medical; Viral Diseases; Virus Diseases; Work; base; body system, hepatic; c myc; c-myc Genes; cardiovascular disorder; cell damage; cell injury; clinical applicability; clinical application; clinical relevance; clinically relevant; design; designing; diagnostic ultrasound; disease/disorder; electric impedance; heavy metal Pb; heavy metal lead; hepatic neoplasia; hepatic neoplasm; hepatopathy; imaging; in vivo; liver disorder; liver tumor; mRNA; malignancy; membrane permeability; neoplasm/cancer; neoplastic; neurodegenerative illness; novel; organ system, hepatic; phase 1 study; phase 1 trial; phase I trial; problem drinker; protocol, phase I; prototype; public health medicine (field); public health relevance; qRTPCR; sonogram; sonography; sonoporation; sound measurement; success; technology development; therapeutic target; tomography; trial regimen; trial treatment; ultrasound; ultrasound imaging; ultrasound scanning; v-myc Avian Myelocytomatosis Viral Oncogene Cellular Homolog; viral infection; virus infection
