A system for genetic editing of a transthyretin (TTR) gene, comprising (i) a Cas12i2 polypeptide or a first nucleic acid encoding the Cas12i2 polypeptide, and (ii) an RNA guide or a second nucleic acid encoding the RNA guide, wherein the RNA guide comprises a spacer sequence specific to a target sequence within an TTR gene. Also provided herein are methods for editing a TTR gene using the gene editing system disclosed herein and/or for treating diseases associated with the TTR gene.

The present disclosure provides nucleic acid molecules comprising a first inverted terminal repeat (ITR), a second ITR, and a genetic cassette encoding a target sequence. In some embodiments, the first ITR and/or the second ITR is an ITR of human bocavirus. Also disclosed are methods of using the nucleic acid molecules in gene therapy applications.

The present disclosure provides codon optimized Factor VIII sequences, vectors, and host cells comprising codon optimized Factor VIII sequences, polypeptides encoded by codon optimized Factor VIII sequences, and methods of producing such polypeptides.

Described herein are engineered nucleases comprising mutations in the cleavage domain (e.g., FokI or homologue thereof) and/or DNA binding domain (zinc finger protein, TALE, single guide RNA) such that on-target specificity is increased.

The present disclosure provides compounds comprising modified oligonucleotides for use in CRISPR. In certain embodiments, such modified oligonucleotides provide improved properties of crRNA. In certain embodiments, such modified oligonucleotides provide improved properties of scrRNA.

The present disclosure provides a canine parvovirus (CPV) nanobody CPV-VHH-H1 and use thereof, belonging to the technical field of immunology. A heavy-chain variable region sequence of the nanobody CPV-VHH-H1 has the amino acid sequence set forth in SEQ ID NO: 1; and a gene encoding the nanobody CPV-VPP-H1 has the nucleotide sequence set forth in SEQ ID NO: 2. In the present disclosure, a nanobody immune library of the CPV is constructed by a phage display technology, a specific anti-CPV nanobody CPV-VHH-H1 is obtained by screening, and it is verified by experiments that the nanobody may specifically bind to the CPV. The present disclosure is expected to develop a new nanobody preparation for use in clinical diagnosis and treatment of the CPV, and provides a certain theoretical reserve for applying the nanobody to the field of veterinary biological products.

This disclosure describes a method that includes using dorsomorphin to increase the infectivity of adeno-associated virus (AAV). The AAV may be of any AAV serotype. In some embodiments, dorsomorphin may be used in combination with IL-6 or TNFα or both. This disclosure further describes methods for using dorsomorphin-treated cells to determine neutralizing antibody (NAb) titers.

The present invention relates to viral vectors that are capable of delivering a heterologous gene to the retina and in particular delivering RLBP1 to RPE and Müller cells of the retina. The invention also relates nucleic acids useful for producing viral vectors, compositions comprising the viral vectors and uses of the compositions and viral vectors. The invention also relates to methods of delivering and/or expressing a heterologous gene to the retina, improving the rate of dark adaption in a subject and treating RLBP1-associated retinal dystrophy.

An object of the present invention is to provide a compound, a method and a pharmaceutical composition for normalizing double homeobox 4 (DUX4) of an individual in which the DUX4 gene has abnormally expressed. Provided is a modified oligonucleotide consisting of 12-30 residues. The modified oligonucleotide includes a nucleobase sequence that includes at least 8 contiguous nucleobase sequences and is complementary to an equal length portion at positions 126-147, 232-248, 1306-1325 or 1472-1495 from a 5′ end of a nucleobase of a mature mRNA of DUX4 of SEQ ID NO: 1. The nucleobase sequence of the modified oligonucleotide has at least 90% complementarity to the equal length portion in the nucleobase sequence of the mature mRNA of DUX4 of SEQ ID NO: 1.

The present invention relates to nucleic acid expression cassettes and vectors containing liver-specific regulatory elements and codon-optimized factor IX or factor VIII transgenes, methods employing these expression cassettes and vectors and uses thereof. The present invention is particularly useful for applications using liver-directed gene therapy, in particular for the treatment of hemophilia A and B.