- RNA and protein synthesis mechanisms
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- RNA Research and Splicing
- DNA and Nucleic Acid Chemistry
- HIV Research and Treatment
- RNA modifications and cancer
- Virus-based gene therapy research
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- HIV/AIDS drug development and treatment
- Circular RNAs in diseases
- CRISPR and Genetic Engineering
- Renal and related cancers
- RNA regulation and disease
- Monoclonal and Polyclonal Antibodies Research
- Molecular Biology Techniques and Applications
- Bacterial Genetics and Biotechnology
- Cancer Genomics and Diagnostics
- Viral Infections and Immunology Research
- Cytomegalovirus and herpesvirus research
- Bacteriophages and microbial interactions
- Cancer Research and Treatments
- DNA Repair Mechanisms
- Bladder and Urothelial Cancer Treatments
University of Lübeck
2009-2021
University Hospital Schleswig-Holstein
2005-2016
Georg Fischer (Switzerland)
2014
German Centre for Cardiovascular Research
2014
Institute of Molecular Biotechnology
2004-2011
Medizinisches Laserzentrum Lübeck (Germany)
2006-2010
Target (Germany)
2009
Target (United States)
2006
German Cancer Research Center
1993-2003
DKFZ-ZMBH Alliance
1992-2003
Genome-wide association studies (GWAS) have identified chromosomal loci that affect risk of coronary heart disease (CHD) independent classical factors. One such signal has been at 6q23.2 in both Caucasians and East Asians. The lead CHD-associated polymorphism this region, rs12190287, resides the 3′ untranslated region (3′-UTR) TCF21, a basic-helix-loop-helix transcription factor, is predicted to alter seed binding sequence for miR-224. Allelic imbalance circulating leukocytes human artery...
Abstract Expression of the 66-kDa form human immunodeficiency virus, type 1 reverse transcriptase in Escherichia coli leads to isolation small amounts a 2 x homodimer and larger heterodimer enzyme which protein is complexed with its carboxyl-terminally truncated 51-kDa form. The latter arises via proteolysis by contaminating proteases. heterodimer, was characterized gel filtration (apparent native molecular mass 120-130 kDa), most active (specific activity, 5000 units/mg, cf. less than 2000...
Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) or their target sites (miR-SNPs) within the 3′-UTR of mRNAs are increasingly thought to play a major role pathological dysregulation gene expression. Here, we studied functional miR-SNPs on miRNA-mediated post-transcriptional regulation First, analyses were performed SNP located miR-155 site Angiotensin II type 1 receptor (AGTR1; rs5186, A > C) mRNA. Second, muscle RAS oncogene homolog (MRAS; rs9818870, C T) mRNA was which is...
ABSTRACT Nonstructural proteins 7 and 8 of severe acute respiratory syndrome coronavirus (SARS-CoV) have previously been shown by X-ray crystallography to form an 8:8 hexadecamer. In addition, it has demonstrated that N-terminally His 6 -tagged SARS-CoV Nsp8 is a primase able synthesize RNA oligonucleotides with length up nucleotides. We present here the 2.6-Å crystal structure feline (FCoV) Nsp7:Nsp8 complex, which 2:1 heterotrimer containing two copies α-helical Nsp7 conformational...
ABSTRACT A 100-fold increase in luciferase activity was observed 293 cells, stably expressing Epstein-Barr nuclear antigen 1 (EBNA1; 293-EBNA1 cells), that had been transiently transfected with plasmids carrying virus (EBV) oriP sequences. This comparison to reporter gene obtained after transfection a plasmid no The on these under the control of either cytomegalovirus immediate-early enhancer-promoter (CMV IE1) or Rous sarcoma promoter. not due replication, since similar enhancement presence...
Various kinds of stress on human cells induce the formation endogenous granules (SGs). Human Argonaute 2 (hAgo2), catalytic core component RNA-induced silencing complex (RISC), can be recruited to SGs as well P-bodies (PBs) indicating that dynamic intracellular distribution hAgo2 in SGs, PBs or at other sub-cellular sites could related efficiency RNA interference (RNAi) machinery. Here, we studied influence heat shock, sodium arsenite (NaAsO2), cycloheximide (CHX) and LipofectamineTM...
Up to now, out of approximately 20 antisense oligodeoxyribonucleotides (as ODN) selected and tested against a given target gene, only one species shows substantial suppression gene expression. In part, this seems be related the general assumption that structures local sequences or nucleic acids are unfavorable for efficient annealing. Experimental approaches find effective as ODN extremely expensive when including large number considering their moderate success. Here, we make use systematic...
The catalytic domain of a hammerhead ribozyme was Incorporated Into 413 nucleotides long antisense RNA directed against the 5′-leader/gag region human immunodeficiency virus type 1 (HIV-1) (pos. +222 to + 634). resulting shown cleave Its target In vitro specifically at physiological ion strength and temperature. We compared antiviral effectiveness this with that corresponding unmodified mutated RNA, which did not substrate vitro. Each these RNAs co-transfected into SW480 cells together...
The use of antisense oligodeoxyribonucleotides (ODN) or ribozymes to specifically suppress gene expression is simple in concept and relies on efficient binding the strand target RNA.Although identification sites accessible base pairing gradually being overcome by different techniques, it remains a major problem ribozyme approaches.In this study we have investigated potential recent experimental theoretical approach predict local accessibility murine DNA-methyltransferase (MTase) mRNA...
Human T-lymphoid cell lines with constitutive intracellular expression of antisense RNA complementary to a 407-bp sequence the 5' leader-gag region human immunodeficiency virus type 1 were established by using nonretroviral vector. In detectable Northern (RNA) hybridization, replication was inhibited 88% 10 days postinfection and this inhibition lasted 3 weeks postinfection.
Abstract The Ki‐67 protein is tightly regulated and depends on the proliferative status of a cell. It present in nuclei proliferating cells but absent resting cells. Since transformation malignant frequently associated with high cell proliferation since labeling index, this antigen may represent potential target for cancer therapy. In study we determined ability phosphorothioate antisense oligodeoxyribonucleotide (ODN) targeted against mRNA to inhibit tumor specifically culture,...
For the biological and therapeutic application of antisense nucleic acids, there is a need to identify effective local target regions given cellular mRNAs or viral single-stranded acids. One critical parameter for effectiveness acids could be potential intramolecular folding sequence element strand strand, respectively. The such subsequences was calculated by using an established secondary structure prediction algorithm. genomic RNA complementary human immunodeficiency virus type 1 (HIV-1),...
In the last decade short interfering RNA (siRNA) became an important means for functional genomics and development of gene-specific drugs. However, major technical hurdles in application siRNA include its cellular delivery followed by intracellular trafficking release order to enter interference (RNAi) machinery. The novel phosphorothioate-stimulated uptake contrasts other known systems because it involves a caveosomal pathway which large amounts are delivered perinuclear environment,...
The length requirements of the antisense portion hammerhead ribozymes for efficacy in living cells was investigated. HIV-1 tat -directed asymmetric ribozyme αYRz195 used with a 195 nt 3′-antisense arm and 3 5′-antisense as well set successively 3′-shortened derivatives thereof. In minimum 20 complementary nucleotides required efficient association 645 target RNA transcript vitro (for all constructs kass ranged between 0.3 1.8 × 10 4 /M/s). cleavage rate constants ( kcleav ) were independent...
Replication of human immunodeficiency virus type 1 (HIV-1) was inhibited by stable intracellular expression antisense RNA in the T-lymphoid cell line Jurkat. When viral subregion encoding HIV-1 activator proteins targeted, extent RNA-mediated inhibition greater than 97% during first 2 weeks postinfection. Later time course, productive infection broke through at high initial infective doses. However, multiplicities equal to or smaller 0.1, production not detectable 5 observation. The results...
Myosin‐heavy‐chain‐specific cDNA clones have been isolated from a library prepared hind leg muscle of 14‐day‐old rabbit. According to restriction enzyme analysis these can be grouped into at least two, probably three different classes. RNA dot‐blot hybridization shows that all correspond mRNAs expressed in fast skeletal muscle. The the most abundant form, class I, aligned cover complete light meromyosin portion myosin heavy chain. sequence coding and 3′‐untranslated region, together...