An aptamer, capable of inhibiting DNA methyltransferase 1 (DNMT1) for use in therapy of diseases characterised by aberrant DNA methylation, e.g. cancer. Method for identifying inhibitors of DNA methyltransferase. An aptamer, capable of inhibiting DNA methyltransferase 1 (DNMT1) for use in therapy of diseases characterised by aberrant DNA methylation, e.g. cancer. SELEX method for identifying aptamers of DNA methyltransferase optionally using 2-fluoro-pyrimindine nucleotide derivatives.

An aptamer, capable of inhibiting DNA methyltransferase 1 (DNMT1) for use in therapy of diseases characterised by aberrant DNA methylation, e.g. cancer. Method for identifying inhibitors of DNA methyltransferase. An aptamer, capable of inhibiting DNA methyltransferase 1 (DNMT1) for use in therapy of diseases characterised by aberrant DNA methylation, e.g. cancer. SELEX method for identifying aptamers of DNA methyltransferase optionally using 2-fluoro-pyrimindine nucleotide derivatives.

The present disclosure provides a novel approach, recomSELEX, that highly integrate mutually supportive recombination and computational methods for aptamer selection and identification. The recomSELEX approach comprises a recombinatorial SELEX platform for aptamer screening that exponentially increases the sequence space that is explored by incorporation of a DNA shuffling step that allows recombination between aptamers. Subsequently, the recombinatorial SELEX platform can also be employed to develop new and optimize already existing aptamers. The recomSELEX further comprises a computational SELEX platform with a constrained genetic algorithm (GA) to identify potential aptamers that are stable and have the desired specificity and affinity of a target.

The present disclosure provides a novel approach, recomSELEX, that highly integrate mutually supportive recombination and computational methods for aptamer selection and identification. The recomSELEX approach comprises a recombinatorial SELEX platform for aptamer screening that exponentially increases the sequence space that is explored by incorporation of a DNA shuffling step that allows recombination between aptamers. Subsequently, the recombinatorial SELEX platform can also be employed to develop new and optimize already existing aptamers. The recomSELEX further comprises a computational SELEX platform with a constrained genetic algorithm (GA) to identify potential aptamers that are stable and have the desired specificity and affinity of a target.

This invention consists of a method for the development of personalized target anticancer therapies based on aptamers and through the systemic modeling of an individual in microfluidic devices. This invention is embodied in microfluidic devices, connections, systems, and methods for the development specific aptamers for the relevant complex biological environment targets. In a first mode, the invention provides methods for the development of target therapies which involves the maintenance of target cancerous cells in co-culture with non-target and non-cancerous cells by using microfluidic devices modularly arranged in closed systems for the development of aptamers. In a second mode, the invention provides a method for the development of target therapies, which includes the maintenance of target cells in co-culture with non-target cells by using microfluidic devices modularly arranged in closed systems. In this case, the invention provides the development of aptamers for the relevant target in homeostatic balance with the components of the fluid conditioned by the co-culture with non-target cells.

This invention consists of a method for the development of personalized target anticancer therapies based on aptamers and through the systemic modeling of an individual in microfluidic devices. This invention is embodied in microfluidic devices, connections, systems, and methods for the development specific aptamers for the relevant complex biological environment targets. In a first mode, the invention provides methods for the development of target therapies which involves the maintenance of target cancerous cells in co-culture with non-target and non-cancerous cells by using microfluidic devices modularly arranged in closed systems for the development of aptamers. In a second mode, the invention provides a method for the development of target therapies, which includes the maintenance of target cells in co-culture with non-target cells by using microfluidic devices modularly arranged in closed systems. In this case, the invention provides the development of aptamers for the relevant target in homeostatic balance with the components of the fluid conditioned by the co-culture with non-target cells.

The invention relates to a method of identifying or producing an aptamer, and a reagent comprising a nucleic acid ligand capable of binding a target sample, wherein the nucleic acid ligand comprises at least one nucleobase modified to contain an azide-alkyne chemical group.

The invention relates to a method of identifying or producing an aptamer, and a reagent comprising a nucleic acid ligand capable of binding a target sample, wherein the nucleic acid ligand comprises at least one nucleobase modified to contain an azide-alkyne chemical group.

The present disclosure relates to a closed loop aptamer development system that identifies one or more aptamers observed experimentally and implements machine-learning models to identify other aptamers not observed experimentally. Particularly, aspects of the present disclosure are directed to receiving a query concerning one or more targets, acquiring a library of aptamers that potential satisfy the query, identifying a first set of aptamers from the library of aptamers that substantially or completely satisfy the query, obtaining sequence data for the first set of aptamers, generating, by a prediction model, a third set of aptamers derived from the sequence data for the first set of aptamers, validating the third set of aptamers that substantially or completely satisfy the query, and upon validating the third set of aptamers and in response to the query, providing the third set of aptamers as a result to the query.

The present disclosure relates to a closed loop aptamer development system that identifies one or more aptamers observed experimentally and implements machine-learning models to identify other aptamers not observed experimentally. Particularly, aspects of the present disclosure are directed to receiving a query concerning one or more targets, acquiring a library of aptamers that potential satisfy the query, identifying a first set of aptamers from the library of aptamers that substantially or completely satisfy the query, obtaining sequence data for the first set of aptamers, generating, by a prediction model, a third set of aptamers derived from the sequence data for the first set of aptamers, validating the third set of aptamers that substantially or completely satisfy the query, and upon validating the third set of aptamers and in response to the query, providing the third set of aptamers as a result to the query.