1,3-Dihydroxyacetone (DHA) is a chemical compound used extensively in the cosmetics industry and with a high prospect of being used in synthesis of new biodegradable polymers if the market price were lower. In this invention, the DHA synthesis from glycerol is carried out photocatalytically under normal conditions using low-cost heterogeneous photocatalysts and easily available oxidizing agents.
Targeted therapy has become a promising therapeutic approach within the last decade due to its reduced toxicity. However, further development of targeted approaches for the specific delivery of therapeutically active substances is required. Especially the targeted delivery of macromolecular charged drug-like molecules, for example antagomirs and siRNA, is limited since these candidates do not cross cell membranes but rather have to be actively provided to the intracellular milieu.
The present invention provides novel aptamers capable of recognizing tumour cells and delivering macromolecular molecules into tumour cells. Aptamers are short single-stranded nucleic acids that recognize specific target structures with high affinity and specificity. Additionally, since aptamers have been shown to possess almost no toxicity and immunogenicity they are promising candidates for biomedical applications.
DNA-methylation (DNAm) of CpG dinucleotides is a key epigenetic process. Upon cell division, the DNAm pattern is maintained on the newly synthesized DNA strand by DNA methyltransferase 1 (DNMT1), whereas DNAm pattern changes are triggered by DNMT3A and DNMT3B that act as de novo methyltransferases.
DNMT3A and DNMT3B play a pivotal role in the epigenetic regulation and development of hematopoietic malignant myeloid disease, such as acute myeloid leukemia (AML) and myelodysplastic syndrome. About 22% of AML patients harbor mutations in DNMT3A, which likely cause the disease. However, little is known about how DNMT3s are epigenetically controlled.
The present invention provides a novel diagnostic and prognostic method for hematopoietic malignant myeloid disease. This method is based on the identification of aberrant hypermethylation at an internal promoter region of DNMT3A, which occurs in about 40% of AML patients.
The present invention provides a safe DTI-antidote able to antagonize the anticoagulant functions of various DTI, such as dabigatran, hirudin, bivalirudin and argatroban.
The exosite structures of thrombin are blocked by complex formation between thrombin and a recently developed aptamer (Müller et al. 2007). As this aptamer does not block the active center of thrombin, the aptamer caged thrombin (Apta-thrombin) retains full reactivity towards DTI but looses its procoagulant functions. This is an important prerequisite to avoid unwanted thrombotic site effects of the DTI antidote.
The ability of apta-thrombin to antagonize the anticoagulant functions of various DTI has been demonstrated in plasma-based studies and in a mouse-model. A prothrombotic response was not induced by apta-thrombin as measured by molecular activation markers. This feature renders apta-thrombin a safe DTI antidote.
The invention describes a CAR which recognizes CD30 as a target antigen and initiates lysis of CD30+ tumor cells but not of CD30+ healthy cells like hematopoietic stem cells. Specific genetic modifications of the
anti-CD30 CAR ensure the specific targeting of CD30+ tumor cells and prevent unwanted side-effects. This approach has been tested in vitro with CD30+ hematopoietic stem cells and CD30+ tumor cells and in vivo in mice transplanted with human CD30+ hematopoietic stem cells. In vivo experiments
proved that the treatment with anti-CD30 T-cells has no unwanted impact on the endogenous immune system.
The present invention provides a novel preventive and therapeutic approach based on the induction of tolerance, which is a key mechanism for the prevention of autoimmunity. The induction of tolerance is achieved through the oral administration of antigen-expressing microorganisms.
In an animal model of multiple sclerosis, the severity and occurrence of the disease symptoms could be significantly reduced by feeding the mice with the safe fodder yeast Candida utilis (Torula yeast) expressing Myelin oligodendrocyte glycoprotein (MOG). Thus, the oral administration of antigen-expressing Candida utilis suppresses the cellular and humoral immune responses taking place in the gut-associated lymphoid tissue. Furthermore, the described treatment is considered to be safe, effective and simple.