A5049231735- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- CRISPR and Genetic Engineering
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Epigenetics and DNA Methylation
- Estrogen and related hormone effects
- Virus-based gene therapy research
- Genomics and Chromatin Dynamics
- RNA regulation and disease
- Chromium effects and bioremediation
- DNA and Nucleic Acid Chemistry
- Cancer Cells and Metastasis
- Metabolism and Genetic Disorders
- Angiogenesis and VEGF in Cancer
- interferon and immune responses
- MicroRNA in disease regulation
- Cancer Genomics and Diagnostics
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- RNA Research and Splicing
- Radiopharmaceutical Chemistry and Applications
- Lymphoma Diagnosis and Treatment
University of Iowa
2015-2025
Wave Life Sciences (United States)
2021-2024
Moderna Therapeutics (United States)
2019-2024
Health Affairs
2022
Duke University Hospital
1999-2012
Duke Medical Center
1999-2012
Duke University
1997-2012
Integrated DNA Technologies (United States)
2012
University of Iowa Hospitals and Clinics
2010
Translational Research Institute
2007
4-1BB is a major costimulatory receptor that promotes the survival and expansion of activated T cells. Administration agonistic anti–4-1BB Abs has been previously shown to enhance tumor immunity in mice. are cell-based products posing significant cost, manufacturing, regulatory challenges. Aptamers oligonucleotide-based ligands exhibit specificity avidity comparable to, or exceeding, Abs. To date, various aptamers have inhibit function their cognate target. Here, we described development an...
The human progesterone receptor (PR) exists as two functionally distinct isoforms, hPRA and hPRB. hPRB functions a transcriptional activator in most cell promoter contexts, while is transcriptionally inactive strong ligand-dependent transdominant repressor of steroid hormone activity. Although the precise mechanism hPRA-mediated transrepression not fully understood, an inhibitory domain (ID) within PR, which necessary for by hPRA, has been identified. Interestingly, although ID present both...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReduction of Chromium(VI) by Ascorbate Leads to Chromium-DNA Binding and DNA Strand Breaks in VitroDiane M. Stearns, Laura J. Kennedy, Kevin D. Courtney, Paloma H. Giangrande, S. Phieffer, Karen E. WetterhahnCite this: Biochemistry 1995, 34, 3, 910–919Publication Date (Print):January 1, 1995Publication History Published online1 May 2002Published inissue 1 January...
Human epidermal growth factor receptor 2 (HER2) expression in breast cancer is associated with an aggressive phenotype and poor prognosis, making it appealing therapeutic target. Trastuzumab, HER2 antibody-based inhibitor, currently the leading targeted treatment for HER2(+)-breast cancers. Unfortunately, many patients inevitably develop resistance to therapy, highlighting need alternative options. In this study, we used a novel, cell-based selection approach isolating 'cell-type specific',...
In humans, the biological response to progesterone is mediated by two distinct forms of receptor (human (h) PR-A, 94 kDa and hPR-B, 114 kDa). These isoforms are transcribed from estrogen-inducible promoters within a single copy PR gene; only difference between them that first 164 amino acids hPR-B (B-upstream sequence) absent in hPR-A. most cell lines such as MCF-7 breast cancer cells), CV-1 (monkey kidney fibroblasts), HeLa cervical carcinoma hPR-A functions transcriptional repressor,...
While microRNAs (miRNAs) clearly regulate multiple pathways integral to disease development and progression, the lack of safe reliable means for specific delivery miRNAs target tissues represents a major obstacle their broad therapeutic application. Our objective was explore use nucleic acid aptamers as carriers cell-targeted miRNA with tumor suppressor function, let-7g. Using an aptamer that binds antagonizes oncogenic receptor tyrosine kinase Axl (GL21.T), here we describe aptamer-miRNA...
RNA aptamers represent an emerging class of pharmaceuticals with great potential for targeted cancer diagnostics and therapy. Several that bind cell-surface antigens high affinity specificity have been described. However, their clinical has yet to be realized. A significant obstacle the adoption is cost manufacturing long sequences through chemical synthesis. Therapeutic are often truncated postselection by using a trial-and-error process, which time consuming inefficient. Here, we used...
Interleukin-10 (IL-10) is a key suppressor of inflammation in chronic infections and cancer. In mice, the inability immune system to clear viral or inhibit tumor growth can be reversed by antibody-mediated blockade IL-10 action. We used modified selection protocol isolate RNA-based, nuclease-resistant, aptamers that bind murine receptor. After 5 rounds high-throughput sequencing (HTS) was analyze library. Using distribution statistics on about 11 million sequences, were identified which...
Background The broad applicability of RNA aptamers as cell-specific delivery tools for therapeutic reagents depends on the ability to identify aptamer sequences that selectively access cytoplasm distinct cell types. Towards this end, we have developed a novel approach combines cell-based selection method (cell-internalization SELEX) with high-throughput sequencing (HTS) and bioinformatics analyses rapidly cell-specific, internalization-competent aptamers. Methodology/Principal Findings We...
Cell-targeted therapies (smart drugs), which selectively control cancer cell progression with limited toxicity to normal cells, have been developed effectively treat some cancers. However, many cancers such as metastatic prostate (PC) yet be treated current smart drug technology. Here, we describe the thorough preclinical characterization of an RNA aptamer (A9g) that functions a for PC by inhibiting enzymatic activity prostate-specific membrane antigen (PSMA). Treatment cells A9g results in...
Abstract Glycogen Storage Disease 1a (GSD1a) is a rare, inherited metabolic disorder caused by deficiency of glucose 6-phosphatase (G6Pase-α). G6Pase-α critical for maintaining interprandial euglycemia. GSD1a patients exhibit life-threatening hypoglycemia and long-term liver complications including hepatocellular adenomas (HCAs) carcinomas (HCCs). There no treatment the current standard-of-care managing (Glycosade ® /modified cornstarch) fails to prevent HCA/HCC risk. Therapeutic modalities...
Abstract Herein, we report the systematic investigation of stereopure phosphorothioate (PS) and phosphoryl guanidine (PN) linkages on siRNA-mediated silencing. The incorporation appropriately positioned configured PS PN to N-acetylgalactosamine (GalNAc)-conjugated siRNAs based multiple targets (Ttr HSD17B13) increased potency durability mRNA silencing in mouse hepatocytes vivo compared with reference molecules clinically proven formats. observation that same modification pattern had...
Full transcriptional activation by steroid hormone receptors requires functional synergy between two domains (AF) located in the amino (AF-1) and carboxyl (AF-2) terminal regions. One possible mechanism for achieving this is a physical intramolecular association (N-) (C-) of receptor. Human progesterone receptor (PR) expressed forms that have distinct activities: full-length PR-B amino-terminally truncated PR-A. generally stronger activator than PR-A, whereas under certain conditions PR-A...