The present invention relates to a method for producing a population of nucleic acids encoding at least one protein comprising at least one immunoglobulin variable domain having a non-human-derived CDR3 amino acid sequence embedded in essentially human framework sequences, as well as to a population of nucleic acids and a population of proteins relates thereto and uses thereof.

Systems, methods, and compositions can be used to generate a therapeutic cell. The system can be an fully closed, automated system. The system, methods and compositions can intake cells of a subject and modify the cells to generate therapeutic cells. Monitoring of the processes of the system and cells can be integrated into the system. Quality control metrics can be used to assess the quality of cells generated and assays to determine quality can be integrated and performed by the closed automated system.

Systems, methods, and compositions can be used to generate a therapeutic cell. The system can be an fully closed, automated system. The system, methods and compositions can intake cells of a subject and modify the cells to generate therapeutic cells. Monitoring of the processes of the system and cells can be integrated into the system. Quality control metrics can be used to assess the quality of cells generated and assays to determine quality can be integrated and performed by the closed automated system.

The present disclosure relates, in general, to methods for improving preparation of a spatial transcriptomics RNA, library, for example a mRNA library, by improving capture of RNA transcript information from a tissue sample in situ. The spatial transcriptomics library from a tissue sample is useful to determine a genetic profile and help diagnose a person who has or is at risk of having a disease, such as cancer, genetic disease, autoimmune disease, and other indications, and improve treatment of the subject.

The present disclosure relates, in general, to methods for improving preparation of a spatial transcriptomics RNA, library, for example a mRNA library, by improving capture of RNA transcript information from a tissue sample in situ. The spatial transcriptomics library from a tissue sample is useful to determine a genetic profile and help diagnose a person who has or is at risk of having a disease, such as cancer, genetic disease, autoimmune disease, and other indications, and improve treatment of the subject.

The present disclosure provides an autologous cell therapy for treating a cancer. Transarterial tirapazamine embolization (TATE) therapy induces tumor necrosis, which, in combination with anti-PD-1 therapy, enhances the efficacy of anti-PD-1 through TATE-induced expansion of anti-tumor T cells activated by the anti-PD-1 antibody. PBMCs collected from TATE and PD-1-treated patients for RNA and DNA extraction and next generation sequencing (NGS) analysis of complementarity region-3 of the TCR from T cell populations in the PBMCs show that clonal expansion of anti-tumor specific T cell receptors (TCRs) occurs. Expansion of the PBMC population for administration to a cancer patient preferentially expands the population of effector T cells targeting the tumor cells without a need for genetic manipulation.

The present disclosure provides an autologous cell therapy for treating a cancer. Transarterial tirapazamine embolization (TATE) therapy induces tumor necrosis, which, in combination with anti-PD-1 therapy, enhances the efficacy of anti-PD-1 through TATE-induced expansion of anti-tumor T cells activated by the anti-PD-1 antibody. PBMCs collected from TATE and PD-1-treated patients for RNA and DNA extraction and next generation sequencing (NGS) analysis of complementarity region-3 of the TCR from T cell populations in the PBMCs show that clonal expansion of anti-tumor specific T cell receptors (TCRs) occurs. Expansion of the PBMC population for administration to a cancer patient preferentially expands the population of effector T cells targeting the tumor cells without a need for genetic manipulation.

The present disclosure provides, inter alia, a novel, functional group-guided method for preparing aptamers for small molecules, including those that cannot be obtained by standard protocols. Also provided are aptamers identified and prepared using the method disclosed herein, compositions comprising such aptamers, and methods and kits for treating a condition using the aptamers and/or compositions disclosed herein.

The present disclosure provides, inter alia, a novel, functional group-guided method for preparing aptamers for small molecules, including those that cannot be obtained by standard protocols. Also provided are aptamers identified and prepared using the method disclosed herein, compositions comprising such aptamers, and methods and kits for treating a condition using the aptamers and/or compositions disclosed herein.

Provided is a novel phase transition adjusting element, a part of which comprises a multivalent phase transition domain, and the remaining comprises at least two ligands, wherein at least one ligand is covalently connected to the part containing the multivalent phase transition structural domain, the remaining ligands are covalently linked to the part comprising the multivalent phase transition structural domain or to other ligands, and each of the at least two ligands can specifically bind to cell surface molecules corresponding thereto. After binding to cell surface molecules, the phase transition adjusting element can effectively enrich cell surface molecules by means of driving phase separation, and enhance the aggregation of cell surface molecules (such as receptor oligomerization), thereby regulating and controlling various cell physiological and biochemical activities, such as receptor downstream signal transmission, cell endocytosis, etc.