The invention provides compositions and methods useful for the treatment and prevention of conditions associated with short telomere length.

Disclosed are compositions and methods that enable loop-mediated isothermal amplification (LAMP) of one or more nucleic acid targets without the need for conventional LAMP primer design customized to each target. A transduction reaction is performed upstream from the LAMP reaction. The transduction reaction generates a single stranded DNA (ssDNA) oligonucleotide when the target nucleic acid is present in the sample. The ssDNA generated in the transduction reaction functions as a required LAMP primer for a universal LAMP template. The ssDNA thus promotes the LAMP reaction. Analysis of the LAMP products can determine the presence of the one or more nucleic acid targets.

Recombinant antibody-based molecules that trigger both T-cell and B-cell immune responses are disclosed. The recombinant molecules are comprised by at least one targeting unit and at least one antigenic unit connected through a dimerization motif. Also disclosed are nucleic acid molecules encoding the recombinant antibody-based molecule and methods of treating multiple myeloma or lymphoma in a patient using the recombinant antibody-based molecules or the nucleic acid molecules.

The present disclosure relates to CRISPR-Cas10 systems and methods for phage genome editing.

This disclosure provides systems, methods, and compositions for site-specific genetic engineering using Programmable Addition via Site-Specific Targeting Elements (PASTE). PASTE comprises the addition of an integration site into a target genome followed by the insertion of one or more genes of interest or one or more nucleic acid sequences of interest at the site. PASTE combines gene editing technologies and integrase technologies to achieve unidirectional incorporation of genes in a genome for the treatment of diseases and diagnosis of disease.

The disclosure provides Moloney murine leukemia virus (MMLV) reverse transcriptase (RTase) mutants. The disclosure as provides suitable amino acid positions in MMLV RTase for mutagenesis and methods and kits for using MMLV RTase mutants to synthesize cDNA from RNA templates.

The present invention provides DNA polymerases that are highly resistant to inhibitors, and that can shorten the entire nucleic acid amplification reaction time by shortening the reverse transcription reaction time in a nucleic acid amplification method, in particular, in PCR or RT-PCR. The DNA polymerase is characterized by having reverse transcription activity, and comprising at least one amino acid modification at position 509 or 744 in SEQ ID NO: 1 or 2. In particular, the amino acid modification at position 509 or 744 in SEQ ID NO: 1 or 2 is substitution with histidine, lysine, or arginine.

The present invention provides novel engineered reverse transcriptase enzymes that afford beneficial improvements in thermal stability, processivity, cDNA yields and elimination of secondary enzymatic activity. The present invention also provides methods for amplifying template nucleic acids using such reverse transcriptase enzymes. This invention addresses deficiencies in the current state of the art reverse transcriptase enzymes in RNA detection and analysis including deficiencies in detection sensitivity, specificity, side enzyme activities, enzyme stability and synthesis capacity, especially when using template nucleic acids ranging in length, secondary structure and nucleotide content.

The present invention relates to a chimeric enzyme comprising a CRISPR class 2 type II enzyme backbone, wherein the HNH domain in the backbone has been replaced, essentially, by a peptide or protein domain having catalytic activity on a single stranded polynucleotide.

The present disclosure provides compositions and methods for conducting prime editing of a target DNA molecule (e.g., a genome) that enables the incorporation of a nucleotide change and/or targeted mutagenesis. The nucleotide change can include a single-nucleotide change (e.g., any transition or any transversion), an insertion of one or more nucleotides, or a deletion of one or more nucleotides. More in particular, the disclosure provides fusion proteins comprising nucleic acid programmable DNA binding proteins (napDNAbp) and a polymerase (e.g., reverse transcriptase), which is guided to a specific DNA sequence by a modified guide RNA, named an PEgRNA. The PEgRNA has been altered (relative to a standard guide RNA) to comprise an extended portion that provides a DNA synthesis template sequence which encodes a single strand DNA flap, which is homologous to a strand of the targeted endogenous DNA sequence to be edited, but which contains the desired one or more nucleotide changes and which, following synthesis by the polymerase (e.g., reverse transcriptase), becomes incorporated into the target DNA molecule. Also disclosed herein are various methods that leverage prime editing, including treating trinucleotide repeat contraction diseases, installing targeted peptide tags, treating prion disease through the installation of protection mutations, manipulating RNA-encoding genes for the installation of RNA tags for controlling the function and expression of RNA, using prime editing to construct sophisticated gene libraries, using prime editing to insert immunoepitopes into proteins, use of prime editing to insert inducible dimerization domains into protein targets, and delivery methods, among others.