Abstract: The present invention provides a gene editing system having reduced off target effects comprising (a) a vector comprising a nucleic acid sequence encoding a nuclease, wherein the nucleic acid encoding the nuclease contains within its sequence a regulatory nucleic acid sequence having a first and second set of splice elements defining a first and second intron, wherein the first and second intron flank a sequence encoding a non-naturally occurring exon sequence containing an in-frame stop codon sequence, and wherein the first and second intron are spliced from the mRNA message to produce an mRNA encoding a non-functional nuclease that contains an amino acid sequence encoded by the non-naturally occurring exon; and (b) an oligonucleotide that binds to the regulatory sequence. Further provided are methods of using the gene editing system of this invention to regulate transgene expression.

Abstract: This invention relates to modified parvovirus capsid proteins with enhanced transduction efficiency, viral vectors comprising the same, and methods of using the same for delivery of nucleic acids to a cell or a subject.

Abstract: This invention relates to viral vectors for delivery of alpha-L-iduronidase to the cornea of a subject and methods of using the same for treatment and prevention of corneal clouding and blindness in a subject due to mucopolysaccharidosis I.

Abstract: Disclosed herein are vectors for delivery of nucleic acid sequence into a target cell. The vectors are non-viral DNA constructs. The vectors have at least one DD-ITR, and complementary copies of the nucleic acid sequence operatively linked to regulatory elements that promote expression. The construct has covalently closed ends having a hairpin structure, and persists within the recipient cells as they divide. Delivery of the vector to the target cell results in sustained expression of the nucleic acid sequences in the target cell. Also disclosed are DNA vector constructs having at least one synthetic ITR, wherein the DNA construct forms linear DNA with hairpin covalently closed ends. Methods of generating the constructs and introducing target cells to thereby promote sustained expression of the nucleic acid sequences contained therein, are also disclosed. Further disclosed are cells and populations thereof, which contain the vectors.

Abstract: The present invention provides a polyploid adeno-associated virus (AAV) capsid, wherein the capsid comprises capsid protein VP1, wherein said capsid protein VP1 is from one or more than one first AAV serotype, wherein said capsid protein VP2 is from one or more than one first AAV serotype and capsid protein VP3, wherein said capsid protein VP3 is from one or more than one second AAV serotype and wherein at least one of said first AAV serotype is different from at least one of said second AAV serotype and is different from at least one of said third AAV serotype, in any combination.

Abstract: This invention relates to modified parvovirus inverted terminal repeats (ITRs) that do not functionally interact with wild-type large Rep proteins, synthetic Rep proteins that functionally interact with the modified ITRs, and methods of using the same for delivery of nucleic acids to a cell or a subject. The modifications provide a novel Rep-ITR interaction that limits vector mobilization, increasing the safety of viral vectors.

Abstract: The presently disclosed subject matter describes the use of fluorinated elastomer-based materials, in particular perfluoropolyether (PFPE)-based materials, in high-resolution soft or imprint lithographic applications, such as micro- and nanoscale replica molding, and the first nano-contact molding of organic materials to generate high fidelity features using an elastomeric mold. Accordingly, the presently disclosed subject matter describes a method for producing free-standing, isolated nanostructures of any shape using soft or imprint lithography technique.

Abstract: The present invention provides a polyploid adeno-associated virus (AAV) capsid, wherein the capsid comprises capsid protein VP1, wherein said capsid protein VP1 is from one or more than one first AAV serotype, wherein said capsid protein VP2 is from one or more than one first AAV serotype and capsid protein VP3, wherein said capsid protein VP3 is from one or more than one second AAV serotype and wherein at least one of said first AAV serotype is different from at least one of said second AAV serotype and is different from at least one of said third AAV serotype, in any combination.

Abstract: As demonstrated herein, a modified recombinant AAV6 vector is provided that transduces the liver and has reduced neutralization of transduction of liver by ADK6 antibody. Accordingly, embodiments of the invention relate to liver tropic rAAV6 vectors that evade neutralization.

Abstract: The present invention provides a polyploid adeno-associated virus (AAV) capsid, wherein the capsid comprises capsid protein VP1, wherein said capsid protein VP1 is from one or more than one first AAV serotype, wherein said capsid protein VP2 is from one or more than one first AAV serotype and capsid protein VP3, wherein said capsid protein VP3 is from one or more than one second AAV serotype and wherein at least one of said first AAV serotype is different from at least one of said second AAV serotype and is different from at least one of said third AAV serotype, in any combination.

Abstract: This invention relates to modified parvovirus inverted terminal repeats (ITRs) that do not functionally interact with wild-type large Rep proteins, synthetic Rep proteins that functionally interact with the modified ITRs, and methods of using the same for delivery of nucleic acids to a cell or a subject. The modifications provide a novel Rep-ITR interaction that limits vector mobilization, increasing the safety of viral vectors.

Abstract: The presently disclosed subject matter describes the use of fluorinated elastomer-based materials, in particular perfluoropolyether (PFPE)-based materials, in high-resolution soft or imprint lithographic applications, such as micro- and nanoscale replica molding, and the first nano-contact molding of organic materials to generate high fidelity features using an elastomeric mold. Accordingly, the presently disclosed subject matter describes a method for producing free-standing, isolated nanostructures of any shape using soft or imprint lithography technique.

Abstract: Disclosed herein are methods and compositions for inhibition of an innate immune response associated with AAV transduction.

Abstract: Disclosed herein is an adeno-associated virus (AAV) particle comprising a surface-bound peptide that enhances transduction of cells across the blood-brain barrier (BBB). Also disclosed herein is a modified AAV capsid protein comprising an insertion of a polypeptide that enhances transduction of cells across the BBB, and an AAV particle comprising the modified AAV capsid protein. Specific peptides are provided. Pharmaceutical formulations and method of administering/delivering a nucleic acid to a cell of the brain and/or central nervous system are also disclosed.

Abstract: Methods and compositions for treating symptoms of conditions such as but not limited to osteoarthritis in horses. The methods may feature direct intraarticular injection of a recombinant self-complementary adeno-associated virus (sc-rAAV) with a vector adapted to express a modified IL-1 Ra peptide. The methods of the present invention may express a therapeutically effective amount of the modified IL-1 Ra peptide so as to ameliorating symptoms associated with the condition being treated.

Abstract: The present invention provides a polyploid adeno-associated virus (AAV) capsid, wherein the capsid comprises capsid protein VP1, wherein said capsid protein VP1 is from one or more than one first AAV serotype, wherein said capsid protein VP2 is from one or more than one first AAV serotype and capsid protein VP3, wherein said capsid protein VP3 is from one or more than one second AAV serotype and wherein at least one of said first AAV serotype is different from at least one of said second AAV serotype and is different from at least one of said third AAV serotype, in any combination.

Abstract: The presently disclosed subject matter describes the use of fluorinated elastomer-based materials, in particular perfluoropolyether (PFPE)-based materials, in high-resolution soft or imprint lithographic applications, such as micro- and nanoscale replica molding, and the first nano-contact molding of organic materials to generate high fidelity features using an elastomeric mold. Accordingly, the presently disclosed subject matter describes a method for producing free-standing, isolated nanostructures of any shape using soft or imprint lithography technique.

Abstract: The present invention provides a polyploid adeno-associated virus (AAV) capsid, wherein the capsid comprises capsid protein VP1, wherein said capsid protein VP1 is from one or more than one first AAV serotype, wherein said capsid protein VP2 is from one or more than one first AAV serotype and capsid protein VP3, wherein said capsid protein VP3 is from one or more than one second AAV serotype and wherein at least one of said first AAV serotype is different from at least one of said second AAV serotype and is different from at least one of said third AAV serotype, in any combination.

Abstract: The presently disclosed subject matter describes the use of fluorinated elastomer-based materials, in particular perfluoropolyether (PFPE)-based materials, in high-resolution soft or imprint lithographic applications, such as micro- and nanoscale replica molding, and the first nano-contact molding of organic materials to generate high fidelity features using an elastomeric mold. Accordingly, the presently disclosed subject matter describes a method for producing free-standing, isolated nanostructures of any shape using soft or imprint lithography technique.

Abstract: This invention relates to modified parvovirus capsid proteins with enhanced transduction efficiency, viral vectors comprising the same, and methods of using the same for delivery of nucleic acids to a cell or a subject.