Compositions of polynucleotide(s) are disclosed. A polynucleotide may encode for a polypeptide, protein, or functional fragment thereof associated with primary ciliary dyskinesia (PCD). Pharmaceutical compositions, kits, and methods for treating a disease or condition associated with cilia maintenance and function, and impaired function of the axoneme are also disclosed. The polynucleotide may be combined with a lipid composition.

Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.

The present invention concerns an in vivo method for introducing a naked mRNA molecule into the cytosol of a cell(s) in a subject, by the use of photochemical internalization, wherein the photosensitising agent is a sulphonated meso-tetraphenyl chlorin, sulfonated tetraphenylporphine or a di- or tetrasulfonated aluminium phthalocyanine used in an amount of 0.000001-0.001 ?g and the cells(s) are contacted with the mRNA molecule and photosensitising agent for 30 seconds to 10 minutes before irradiation of the cell(s). The method may be used to express a polypeptide in the subject. The method is also directed to pharmaceutical compositions containing the photosensitising agents and the mRNA and uses of the molecules in therapy, e.g. to treat or prevent cancer or an infection.

Provided herein are methods and compositions for editing the genome of a cell. In some embodiments, a nucleotide sequence of at least 200 nucleotides in length is inserted into a target region in the genome of a cell.

Described herein is the discovery that HGFs activate the growth and migration of lymphatic endothelial cells and thereby promote lymphangiogenesis. The present invention is based on this finding, and provides lymphangiogenesis-promoting agents comprising as active ingredients HGFs, or proteins or compounds functionally equivalent thereto. Based on the finding described above, the present invention also provides methods for promoting lymphangiogenesis which comprise the step of locally administering HGFs or proteins functionally equivalent thereto to affected areas in patients with lymphedema.

The present disclosure relates to: an adipocyte-targeting non-viral gene delivery complex comprising a sh(FABP4+FABP5) dual plasmid vector; and treatment for obesity and obesity-induced metabolic syndromes by using the same and, more particularly, to a gene delivery complex comprising: an adipocyte-targeting sequence; a nine-arginine (R9) peptide; and a dual plasmid vector comprising a gene for treatment of obesity and obesity-induced metabolic syndromes, wherein the gene for treatment of obesity and obesity-induced metabolic syndromes is a base sequence inhibiting the expression of a FABP4 gene and a FABP5 gene. According to the present disclosure, in order to treat obesity-related diseases, a dual plasmid vector capable of simultaneously inhibiting the FABP4 and FABP5 genes is produced, and this vector is bound to a predetermined delivery system that specifically delivers the vector into adipocytes so as to provide a gene delivery complex. In this way, it is possible to achieve an excellent therapeutic effect on obesity which targets only adipocytes without cytotoxicity.

Chimeric antigen receptors containing CD33 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

The present invention involves nucleic acid vectors (e.g., circular DNA vectors) and compositions thereof. Also provided herein are methods of administering nucleic acid vectors (e.g., circular DNA vectors) and compositions thereof, e.g., in combination with pulsed electric field therapy.

Disclosed herein are methods of delivering an agent to a subject. Further disclosed herein are methods of treating a disease or disorder in a subject. The methods may include administering to the subject a chondroitinase polypeptide or a polynucleotide encoding a chondroitinase polypeptide in an amount sufficient to degrade glycosaminoglycans, and administering to the subject the agent. The methods may further include administering a hyaluronidase polypeptide or a polynucleotide encoding a hyaluronidase.

Provided herein are methods, compounds, and compositions useful for targeted delivery of compounds to non-native cells ectopically expressing cell surface receptors. Such methods, compounds, and compositions are useful, for example, in gene therapy mediated ectopic expression of cell surface receptors and targeted delivery of compounds, such as conjugated oligonucleotides, to the non-native cells ectopically expressing cell surface receptors. Such methods, compounds, and compositions can be useful, for example, to treat, prevent, delay or ameliorate disease in an individual by targeted reduction of a gene of interest in the non-native cell ectopically expressing cell surface receptors.