Compositions and regimens useful in treating hemophilia B are provided. The method involves administering to the human subject via a peripheral vein by infusion of a suspension of replication deficient recombinant adeno-associated virus (rAAV).

Compositions are disclosed which include a CAQK peptide linked or conjugated to a cargo composition, where the peptide selectively homes the composition to a site of nervous system injury in a subject.

The present invention relates to improved adeno-associated virus (AAV) particles for gene delivery and gene therapy. Provided are adeno associated virus (AAV) particles that comprise a modified capsid. The present invention further relates to methods for producing the improved AAV particles of this invention by removing natural binding sites in adeno associated virus (AAV) capsids and introducing ligand binding sites into said capsid to provide AAVs that transduce only particular cells of interest. An additional aspect of the present invention relates to modified AAV particles for use in the treatment of a disease and methods for treating a disease, comprising administering the modified AAV particles to a subject in need thereof. Yet a further aspect of this invention relates to the AAV particles of this invention for the transfection of cells, for example as a gene delivery tool in basic research.

Compositions and methods for treatment of CEP290 related diseases are disclosed.

The disclosure features target cell delivery lipid nanoparticle (LNP) compositions that allow for enhanced delivery of agents, e.g., nucleic acids, such as therapeutic and/or prophylactic RNAs, to target cells, in particular liver cells and/or splenic cells. The LNPs comprise an effective amount of a target cell delivery potentiating lipid such that delivery of an agent by a target cell target cell delivery LNP is enhanced as compared to an LNP lacking the target cell delivery potentiating agent. Methods of using the target cell target cell delivery LNPs for delivery of agents, e.g., nucleic acid delivery, for protein expression, and for modulating target cell activity are also disclosed.

The disclosure provide methods and compositions that use gene editing or gene therapy to treat alpha thalassemia major. The gene editing may be performed ex vivo in fetal cells or cells obtained after birth to improve production of globin, with those cells then delivered to the fetus. In other embodiments, gene editing reagents are delivered to the fetus or the patient after birth in vivo to edit genes of the alpha-globin cluster and improve globin production. Gene editing system such as CRISPR, TALENs, or ZFNs are used to increase production of alpha, zeta, or theta globin and/or to decrease production of gamma globin. Globin production may be improved by inserting a copy of globin gene or mutating a globin gene to change its expression. Any of the gene editing strategies may be performed in conjunction with delivering to a fetus or patient after birth a therapeutic blood transfusion. Exemplary patients after birth are patients no older than one year of age.

This disclosure provides methods and pharmaceutical compositions for attenuating immune response in a subject suffering from a genetic disorder and receiving gene or nucleic acid therapy. The pharmaceutical compositions and formulations may include immunosuppressants, such as protein kinase inhibitors, including tyrosine kinase inhibitors (TKIs), in conjunction with various types of therapeutic nucleic acids (TNAs) and carriers (e.g., lipid nanoparticles).

The present disclosure provides methods and compositions for facilitating efficient adeno-associated virus (AAV)-based homologous recombination (HR). Subject methods include a step of contacting a cell (e.g., a population of cells) with a ribonucleotide reductase inhibitor, which provides for increased HR efficiency compared to performing HR in the absence of the inhibitor. The cell is also contacted with a recombinant adeno-associated vims (rAAV) that includes a donor DNA having a sequence cassette (i.e., a nucleotide sequence of interest) flanked by homology arms that facilitate integration of the sequence cassette into a target genomic locus via HR.

Disclosed herein, in certain embodiments, are recombinant Arc and endogenous Gag polypeptides, and methods of using recombinant Arc and endogenous Gag polypeptides.

An object of the present invention is to provide a lipid composition capable of achieving excellent nucleic acid delivery for a wide variety of nucleic acids. According to the present invention, there is provided a lipid composition containing a first lipid which is a lipid represented by Formula (1) or a salt thereof, sterols, and nucleic acid, in which a ratio of the number of moles of the first lipid in the lipid composition to the number of moles of sterols in the lipid composition is 0.300 or more and less than 1.299.

##STR00001##

In the formula, X represents —NR.sup.1— or —O—, R.sup.1 represents a hydrogen atom, a hydrocarbon group, or the like, R.sup.2 and R.sup.3 each independently represent a hydrogen atom, a hydrocarbon group, or the like, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.11, and R.sup.12 each independently represent a hydrogen atom or an alkyl group, groups in any one or more pairs among R.sup.4 and R.sup.5, R.sup.10 and R.sup.5, R.sup.5 and R.sup.12, R.sup.4 and R.sup.6, R.sup.5 and R.sup.6, R.sup.6 and R.sup.7, R.sup.6 and R.sup.10, R.sup.12 and R.sup.7, and R.sup.7 and R.sup.8 may be linked to each other to form a 4- to 7-membered ring which may contain an O atom, a, b, c, and d are each independently represent an integer of 0 to 3, a+b is 1 or more, and c+d is 1 or more.