Abstract: Genomic insertions, duplications, and insertion/deletion (indels) account for ˜14% of human pathogenic mutations. Current gene editing methods cannot accurately or efficiently correct these abnormal genomic rearrangements, especially larger alterations (>100 bp). The presently disclosed compositions and methods accurately delete insertions/duplications and repair the deletion junction to improve the scope of gene therapies. For example, a Cas9 prime editor (PECas9) is combined with two prime editing guide RNAs (pegRNAs) targeting complementary DNA strands. PECas9 can replace an ˜1-kb genomic fragment with a desired sequence at the target site without requiring an exogenous DNA template.

Abstract: Molecular constructs and dual recognition constructs having a sequence encoding a TCR affinity weakening motif, and DNA and RNA sequences corresponding thereto, are presented. Modified T-cells and other cells transformed with the molecular contracts express a modified TCR that imparts a reduction, in non-specific binding, -an enhancement of binding specificity and an enhancement of binding affinity for a target antigen, compared to non-transformed (wild-type, native) T-cells, are described. The modified TCRs possess an affinity enhancing motif and an affinity weakening motif. Methods of transforming cells and methods of using enriched populations of transformed cells, in the treatment of cancer and infections arid T-cell mediated pathologies are provided. The affinity weakening motif imparts a weakened interaction, of a TCR with major histocompatibility complex proteins, such as HLA proteins in humans.

Abstract: Molecular constructs and dual recognition constructs having a sequence encoding a TCR affinity weakening motif, and DNA and RNA sequences corresponding thereto, are presented. Modified T-cells and other cells transformed with the molecular contracts express a modified TCR that imparts a reduction, in non-specific binding, an enhancement of binding specificity and an enhancement of binding affinity for a target antigen, compared to non-transformed (wild-type, native) T-cells, are described. The modified TCRs possess an affinity enhancing motif and an affinity weakening motif. Methods of transforming cells and methods of using enriched populations of transformed cells, in the treatment of cancer and infections arid T-cell mediated pathologies are provided. The affinity weakening motif imparts a weakened interaction, of a TCR with major histocompatibility complex proteins, such as HLA proteins in humans.

Abstract: High-affinity variants of the DMF5 TCR, and methods of use thereof for the treatment and imaging of cancer in a patient.

Abstract: High-affinity variants of the DMF5 TCR, and methods of use thereof for the treatment and imaging of cancer in a patient.

Abstract: Described are techniques for optical detection of single molecule signals from a nanopore array for analysis of nucleic acid sequences. These techniques are useful for rapid multiplexed DNA sequencing.

Abstract: Described herein are inexpensive high throughput methods to convert a target single stranded DNA (ssDNA) such that each nucleotide (or base) adenine (A), thymine (T), guanine (G) and cytosine (C) is converted to a pre-determined oligonucleotide code, with the sequential order preserved in the converted ssDNA, or RNA. The method does not require the use of DNA polymerases during the cycles and involves the use of an oligonucleotide probe library with repeated cycles of ligation and cleavage. At each cycle, one or more nucleotides on one end (e.g., either the 5? end or the 3? end) of a target, e.g., ssDNA, are cleaved and then ligated with the corresponding oligonucleotide code at the other end of the target ssDNA.

Abstract: The present invention is directed to a high throughput method for producing a large number of different antibodies, more specifically organized antibody microarrays. These antibodies and antibody microarrays can be used to rapidly assay protein abundance and identify types of proteins that are expressed in cells and tissues under a variety of conditions, or to compare protein expression profiles of different cells.

Abstract: Improved methods for designing molecular conjugate therapeutics are described. Antibodies are described having specificity for a targeting antigen, said antigen comprising one or more MHC-binding peptides bound to a corresponding class I MHC molecule. When linked to a label or toxic agent, the resulting antibody conjugate can be used for diagnosis, imaging and for treatment against pathogens.