This invention relates to functional ligands to target molecules, particularly to functional nucleic acids and modifications thereof, more particularly to functional ligands with binding affinity to metabolites of nerve agents, and further particularly to functional ligands with binding affinity to metabolites of VX-acid (metabolite of VX nerve agent) and GB-acid (metabolite of sarin nerve agent).

The present disclosure provides methods and compositions for genetically modifying lymphocytes, for example T cells and/or NK cells, in shorter times than previously and/or in whole blood or a component thereof. In some embodiments a lymphodepletion filter assembly is used before or after forming a reaction mixture where lymphocytes are contacted with recombinant retroviral particles in a closed system, to genetically modify the lymphocytes.

The invention relates to a DNA aptamer that can inhibit the enzymatic activity of tyrosinase for the conversion of tyrosine into L-DOPA and dopaquinone, and to the dermatological and cosmetic uses thereof.

This invention provides for products and processes for binding to a preselected target, where the process involves contacting this target to an oligonucleotide molecule that contains one or more “non-standard” nucleotides, which are nucleotide analogs that, when incorporated into oligonucleotides (DNA or RNA, collectively xNA), present to a complementary strand in a Watson-Crick pairing geometry a pattern of hydrogen bonds that is different from the pattern presented by adenine, guanine, cytosine, and uracil. This disclosure provides an example where such an oligonucleotide molecule contains a single 2-amino-8-(1′-β-D-2′-deoxyribofuranosyl)-imidazo[1,2-a]-1,3,5-triazin-4(8H)one and a single 6-amino-5-nitro-3-(1′-β-D-2′-deoxyribofuranosyl)-2(1H)-pyridone, and where the target is a cell, and is obtained by a process of in vitro selection.

Systematic Evolution of Ligand Exponential Enrichment (SELEX) is involved to screen DNA/RNA aptamers that recognize a target molecule (including biomolecules such as nucleic acids, lipids, sugars, proteins, and peptides, hormones, low molecular weight chemical substances, toxic substances, ions, etc.). In general, in order to perform SELEX, a process of fixing a target molecule on a substrate or bead surface is required. In addition, since positive/negative monitoring is not possible in each round of a SELEX process to observe whether an aptamer library is actually well combined with a target substance, whether the SELEX process is proceeded correctly is checked by analyzing aptamers screened through several rounds. In order to remarkably solve these conventional problems and to construct a simpler and easier SELEX technique, the present disclosure provides a new SELEX technique using gold nanoparticles.

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.

Provided herein are single guide RNAs (sgRNAs) that comprise aptamer sequences and related compositions and methods. Also provided herein are methods of selecting inducible sgRNAs that comprise aptamer sequences.

The present disclosure provides methods for genetically modifying lymphocytes and methods for performing adoptive cellular therapy that include transducing T cells and/or NK cells. The methods can include inhibitory RNA molecule(s) and/or engineered signaling polypeptides that can include a lymphoproliferative element, and/or a chimeric antigen receptor (CAR), for example a microenvironment restricted biologic CAR (MRB-CAR). Additional elements of such engineered signaling polypeptides are provided herein, such as those that drive proliferation and regulatory elements therefor, as well as replication incompetent recombinant retroviral particles and packaging cell lines and methods of making the same. Numerous elements and methods for regulating transduced and/or genetically modified T cells and/or NK cells are provided, such as, for example, those including riboswitches, MRB-CARs, recognition domains, and/or pH-modulating agents.

Compositions and methods for preparing and identifying aptamers and aptamer-protein conjugates are provided. The use of a nucleotide analog functionalized with an amine-reactive cross-linker facilitates covalent cross-linking of the aptamer to a protein, in particular site-specific cross-linking to the Fc domain of an antibody.