Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

An exemplary composition can be provided which includes an identified substance that induced cell reprogramming. Cells can also be provided having pluripotency having high safety when applied to regenerative medicine, using the composition, and a production method therefor. A cell reprogramming-inducing composition can include at least one 30S ribosome protein selected from the group consisting of 30S ribosome protein S2, 30S ribosome protein S8 and 30S ribosome protein S15 as a substance that reprograms cells derived from a mammalian animal is provided. Further, an exemplary production method for cells having pluripotency from somatic cells using the composition can be provided.

An object of the present invention is to provide a novel method for designing a primer ensuring reactivity and discriminatory power in a method for detecting a single base substitution based on an ASP-PCR method and to provide a method for easily detecting multiple point mutations within overlapping amplicons, particularly, two adjacent single base substitutions. The single base substitutions can easily be detected by using a mutant primer in which the base of the third nucleotide from the 3′ end corresponds to the base of a mutant nucleotide of a single base substitution contained in a nucleic acid sample, in which the base of the second nucleotide from the 3′ end is not complementary to the base of the corresponding nucleotide of the nucleic acid, and in which the bases of the other nucleotides are complementary to the bases of the corresponding nucleotides of the nucleic acid.

An object of the present invention is to provide a novel method for designing a primer ensuring reactivity and discriminatory power in a method for detecting a single base substitution based on an ASP-PCR method and to provide a method for easily detecting multiple point mutations within overlapping amplicons, particularly, two adjacent single base substitutions. The single base substitutions can easily be detected by using a mutant primer in which the base of the third nucleotide from the 3′ end corresponds to the base of a mutant nucleotide of a single base substitution contained in a nucleic acid sample, in which the base of the second nucleotide from the 3′ end is not complementary to the base of the corresponding nucleotide of the nucleic acid, and in which the bases of the other nucleotides are complementary to the bases of the corresponding nucleotides of the nucleic acid.

The present invention aims to provide a modified Cas9 protein with relaxed restriction on target sequence while maintaining binding ability to guide RNA, and use thereof. A protein containing the amino acid sequence of SEQ ID NO: 1 in which the 1335-position arginine is mutated into alanine (R1335A), isoleucine (R1335I), methionine (R1335M), threonine (R1335T) or valine (R1335V), the 1111-position leucine is mutated into arginine (L1111R), the 1135-position aspartic acid is mutated into valine (D1135V), the 1218-position glycine is mutated into arginine (G1218R), the 1219-position glutamic acid is mutated into phenylalanine (E1219F), the 1322-position alanine is mutated into arginine (A1322R), and the 1337-position threonine is mutated into arginine (T1337R), and the like.

The present invention provides an approach to enhancing the production of a foreign protein serving as a protein-based pharmaceutical product in host cells such as cultured cells derived from a mammal. The present invention provides transformed cells having a novel Hspa5 gene promoter, and a method for secreting and producing a foreign protein at high levels using the transformed host cells.

The present invention provides an approach to enhancing the production of a foreign protein serving as a protein-based pharmaceutical product in host cells such as cultured cells derived from a mammal. The present invention provides transformed cells having a novel Hspa5 gene promoter, and a method for secreting and producing a foreign protein at high levels using the transformed host cells.

The present invention is directed to viral vectors and methods of their production and use.

A human tissue stem cell in which a gene of interest is introduced into a gene locus of a stem cell marker gene.

Compositions and methods for gene editing. In some embodiments, a polynucleotide encoding Cas9 is provided that can provide one or more of improved editing efficiency, reduced immunogenicity, or other benefits.