Disclosed are methods and pharmaceutical compositions for treating and inhibiting conical vascularization including conical vascularization associated with viral infection, chemical injury, autoimmune conditions, and post-corneal transplantation or in subjects having a PAX6 mutation associated with conical vascularization. The methods and pharmaceutical compositions are utilized in administering treatment that results in increased concentration of FOXC1 in a subject's cornea in order to treat or inhibit corneal vascularization.

Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of retinal cells as compared to the infectivity of the retinal cells by an AA V virion comprising the unmodified parental capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and in clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more cells of the retina for the treatment of retinal disorders and diseases.

Disclosed are compositions for delivering gene editing molecules to a cell. Exemplary compositions comprise a micelle assembled from a plurality of triblock copolymers, wherein each triblock copolymer having at least one hydrophobic block, at least one hydrophilic block, and at least one poly(L-histidine) block, wherein: the at least one poly(L-histidine) block complexes with the at least one gene editing molecule; and the at least one poly(L-histidine) block is capable of a pH dependent release of the at least one gene editing molecule.

Provided herein are methods of administering gapmer oligomeric compounds with GalNAc conjugate groups to a human.

The present invention discloses a method for treating or preventing hereditary retinal dystrophy, the method comprising: administering a composition comprising a RIP1 inhibitor or a MLKL inhibitor to a subject in need thereof. The RIP1 inhibitor is, for example, RIPA-56, and the MLKL inhibitor is, for example, GW806742X.

Compositions and methods concern the sequence modification of an endogenous genomic DNA region. Certain aspects relate to a method for site-specific sequence modification of a target genomic DNA region in cells comprising: transfecting the cells by electroporation with a composition comprising (a) a DNA oligo; (b) a DNA digesting agent; and (c) a targeting RNA, wherein the targeting RNA is capped and/or polyadenylated; wherein the donor DNA comprises: (i) a homologous region comprising nucleic acid sequence homologous to the target genomic DNA region and (ii) a sequence modification region; and wherein the genomic DNA sequence is modified specifically at the target genomic DNA region.

Methods for modifying a dystrophin gene are disclosed, for restoring dystrophin expression within a cell having an endogenous frameshift or nonsense mutation within the dystrophin gene. The methods comprise introducing a first cut within an exon en or intron of the dystrophin gene creating a first exon end or intron end, wherein said first cut is located upstream of the endogenous frameshift or nonsense mutation; and introducing a second cut within an exon or intron of the dystrophin gene creating a second exon end or intron end, wherein said second cut is located downstream of the frameshift or nonsense mutation. Upon joining/ligation of said first and second exon ends or intron ends a hybrid exon or intron junction is created and dystrophin expression is restored, as the correct reading frame is restored. Reagents and uses of the method are also disclosed, for example to treat a subject suffering from muscular dystrophy.

Provided herein, inter alia, are methods and compositions directed to suppressing tumor cell growth in a subject as well as methods for sensitizing a proliferating cell for treatment with a cytotoxic agent via inhibiting expression of HE4 and one or more immune checkpoint inhibitors (ICIs). Also provided herein are methods for determining whether a subject who has been diagnosed with cancer would benefit from immunotherapy as well as methods for determining whether a subject with cancer is responding to immunotherapy via assessment of levels of HE4 gene and/or protein expression.

The invention provides a method for generating an oligonucleotide with which an axon may be skipped in a pre-mRNA and thus excluded from a produced mRNA thereof. Further provided are methods for altering the secondary structure of an mRNA to interfere with splicing processes and uses of the oligonucleotides and methods in the treatment of disease. Further provided are pharmaceutical compositions and methods and means for inducing skipping of several axons in a pre-mRNA.

The invention provides a method for generating an oligonucleotide with which an exon may be skipped in a pre-mRNA and thus excluded from a produced mRNA thereof. Further provided are methods for altering the secondary structure of an mRNA to interfere with splicing processes and uses of the oligonucleotides and methods in the treatment of disease. Further provided are pharmaceutical compositions and methods and means for inducing skipping of several exons in a pre-mRNA.