The invention provides systems and methods for discovering candidate therapies for genetic conditions and also for screening those therapies in vitro for evidence of neurotoxicity. Where a medical condition is a consequence of a genetic target such as a mutated gene, the disclosure provides in silico methods to generate lists of candidate sequences for antisense oligonucleotides (ASOs) that will potentially bind to the gene or transcripts from the gene in vivo and treat the associated condition by restoring a healthy phenotype of gene expression. The invention provides in vitro methods for screening candidate ASO sequences for symptoms of neurotoxicity in vivo. For example, candidate sequences that are output by the in silico analytical pipeline can be synthesized and assayed against live cells in vitro.

The present invention includes compositions and methods comprising viral vector systems for multiplexed activation of endogenous genes as immunotherapy and viral-based immune-gene therapy.

A biological library that includes a plurality of cryo-silicified cells, a plurality of dehydrated cryo-silicified cells, or both, where the cryo-silicified cells and/or the dehydrated cryo-silicified cells contain accessible biological information. In some embodiments, the biological information includes genetic information, proteomic information, or transcriptomic information. Members of the library may be analyzed to identify changes in the biological information associated with a medical condition or response to treatment. When the library includes B lymphocytes, cellular material from the B lymphocytes may be used to produce an antibody.

Provided herein are polypeptides comprising a modified fibronectin type III (Fn3) domain, wherein the amino acid corresponding to residue 58 of SEQ ID NO: 1 is mutated, and wherein the solubility is enhanced relative to the solubility of a Fn3 domain in which the amino acid corresponding to residue 58 of SEQ ID NO: 1 is not mutated. Also provided are libraries comprising a plurality of the polypeptides and a method for identifying a polypeptide that binds to a target.

The present invention provides an aptamer that specifically hinds CD44, composition comprising the aptamer, as well as methods for detecting CD44 and for targeted delivery to CD44-expressing cells.

The invention relates to a nucleic acid molecule comprising: a. a first region comprising a nucleic acid sequence coding for the protein Cyclin D1, also called CCND1, said first region being controlled by means allowing the expression of said protein, and b. at least one second region, said second region comprising essentially a sequence from 14 to 59 nucleic acids, said second region corresponding to a transcribed region of a gene, said second region containing at least a genetic modification compared to the same region of the corresponding wild-type version of said gene, said second region being genetically isolated from the means allowing the expression of said protein such that said second region is not translated into a peptide.

A hybrid guide RNA (hgRNA) comprising a proximal spacer, a distal spacer, a type II CRISPR-Cas tracrRNA, and a type V CRISPR-Cas direct repeat. Also provided herein are further multiplexed hgRNAs comprising additional direct repeats and spacers as well as methods of making and using thereof. Libraries comprising said hgRNAs or components thereof, cells, kits and reagents employed in the making or use thereof are also provided.

The technology relates in part to methods and compositions for analyzing nucleic acid. In some aspects, the technology relates to methods and compositions for preparing a nucleic acid library from single-stranded nucleic acid fragments.

The present invention relates functional ligands to target molecules, particularly to functional nucleic acids and modifications thereof, and to methods for simultaneously generating, for example, numerous different functional biomolecules, particularly to methods for generating numerous different functional nucleic acids against multiple target molecules simultaneously. The present invention further relates to functional ligands which bind with affinity to target molecules, such as antibiotics, such as colistin.

The present disclosure provides a high-throughput screening system and method for identification of novel drugs and drug targets. The method enables large-scale analysis of interactions between allogeneic pairs of target cells and immune cells by using an immune-bridge protein, library of guide RNA, and/or 3D tumor model.