Disclosed are compositions and methods for targeted treatment of TLR9-expressing cancers, such as primary human MDS progenitors and hematopoietic stem cell (HSC), as well as lung and breast cancers. In particular, multispecific, multivalent antibodies are disclosed that are able to engage T-cells to destroy TLR9-expressing malignant cells.

Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.

The present invention provides compositions comprising mRNA molecules encapsulated within lipid particles. The lipid particles comprise a cationic lipid, a non-cationic lipid, and an mRNA molecule that is encapsulated within the lipid particle. The compositions are useful, for example, to introduce the mRNA molecules into a human subject where they are translated to produce a polypeptide that functions to ameliorate one or more symptoms of a disease. The invention also provides cationic lipids that are useful for preparing the compositions of the invention.

The present disclosure provides compositions comprising an opsin polypeptide and an arrestin polypeptide and their use thereof. Exemplary embodiments provide a composition including an opsin polypeptide, or an opsin polypeptide and an arrestin polypeptide, wherein at least one of the opsin or arrestin polypeptide comprises at least one mutation that increases a temporal resolution of the opsin polypeptide’s response to light. The opsin polypeptide and the arrestin polypeptide can be operably linked or separate. Additionally, use of said compositions for restoring retinal photosensitivity or treating a retinal degenerative condition is also provided.

The present disclosure provides, among other aspects, codon-altered polynucleotides encoding Factor VIII variants for expression in mammalian cells. In some embodiments, the disclosure also provides mammalian gene therapy vectors and methods for treating hemophilia A.

The present invention relates to improved therapies for the treatment of heart disease, particularly the improved delivery of therapeutic agents to heart tissue by direct infusion into the coronary circulation. A preferred embodiment of the invention is a method of treating or preventing a cardiovascular disease by transfecting cardiac cells of a large mammal, the method comprising, identifying a mammal in need of treatment or prevention of heart disease, supplying NO to the coronary circulation prior to, and/or during the infusion of a therapeutic polynucleotide into a blood vessel of the coronary circulation in vivo, where the therapeutic polynucleotide is infused into the blood vessel over a period of at least about three minutes, where the coronary circulation is not isolated or substantially isolated from the systemic circulation of the mammal; and where the therapeutic polynucleotide transfects cardiac cells of the animal resulting in the treatment or prevention of the heart disease.

Cell based therapy comprises administration to the lung by injection into the blood system of viable, mammalian cells effective for alleviating or inhibiting pulmonary disorders. The cells may express a therapeutic transgene or the cells may be therapeutic in their own right by inducing regenerative effects.

The present invention provides a compound represented by the formula (Ia) as a novel cationic lipid that forms a lipid particle and also provides a lipid particle comprising the compound. The present invention further provides a nucleic acid lipid particle containing the lipid particle, and a pharmaceutical composition containing the nucleic acid lipid particle as an active ingredient.

The invention relates to the field of andeno-associated virus (AAV) based gene therapy, in particular to the use of a combination of recombinant AAV-transgene vectors with an immunosuppressant and/or empty-AAV capsids. The invention further provides a composition and a kit of parts based on this combination.

The present invention relates to regulatable adeno-associated virus (AAV) vectors as well as to their use in gene therapy. It further relates to corresponding nucleic acid molecules, host cells, non-human transgenic animals, pharmaceutical compositions and kits.