Abstract: Methods of employing oncolytic viruses and focused ultrasound, e.g., for focal delivery to the mammalian brain, are provided.

Abstract: Methods of employing non-oncolytic viruses or plasmids and focused ultrasound are provided. Specifically, the disclosure provides methods for ultrasound-mediated non-invasive delivery of gene therapy agents to the central nervous system, wherein magnetic resonance (MR) guided focused ultrasound is used, optionally in combination with microbubbles, to facilitate gene delivery to a particular region of the brain.

Abstract: Methods and compositions for controlling visceral organ function are provided. For example, the methods and compositions are useful to prevent, inhibit or treat disease as a result of controlling, e.g., regulating, organ function. In one embodiment, viral vectors are delivered to an organ, and the virus infects a nerve that regulates a function of the organ. In one embodiment, the vial vector is a retrograde vector. In one embodiment, the viral vector encodes a gene product, the activity of which is controlled by an exogenously delivered agent or energy. The delivery of the agent or energy thus controls the organ function.

Abstract: A fluid infusion device and a method of using the same. The device includes an outer, flexible guide catheter having a distal end for introduction beneath the skull of a patient and a proximal end remaining external of the patient. A flexible infusion fiber is located within the guide catheter and has a distal end extending outwardly from the guide catheter to be located in a target area within the patient's brain. The infusion fiber can be fixed or axially movable within the guide catheter. In the latter embodiment, the proximal end of the infusion fiber extending outwardly from the guide catheter can be manipulated to locate the distal end of the infusion fiber in the target area. An infusion pump is connected to the proximal end of the infusion fiber to infuse a minute quantity of fluid at an extremely low flow rate into the brain of the patient.

Abstract: Sequences are provided that are capable of directing circular adeno-associated virus replication, useful in vectors for providing therapeutic agents to a subject in need thereof. The vectors of the invention are particularly useful in the treatment of acute medical conditions requiring rapid gene expression. Further provided are methods for producing packaged defective viral vectors.

Abstract: Sequences are provided that are capable of directing circular adeno-associated virus replication, useful in vectors for providing therapeutic agents to a subject in need thereof. The vectors of the invention are particularly useful in the treatment of acute medical conditions requiring rapid gene expression. Further provided are methods for producing packaged defective viral vectors.

Abstract: The present invention describes a method of identifying inducible genetic regulatory sequences that can control the transcription of specific gene transcripts. Methods of using inducible genetic regulatory sequences are also discussed. In particular, the genetic regulatory sequences of the present invention can modulate the transcription of a nucleic acid transcript in vivo.

Abstract: A fluid infusion device and a method of using the same. The device includes an outer, flexible guide catheter having a distal end for introduction beneath the skull of a patient and a proximal end remaining external of the patient. A flexible infusion fiber is located within the guide catheter and has a distal end extending outwardly from the guide catheter to be located in a target area within the patient's brain. The infusion fiber can be fixed or axially movable within the guide catheter. In the latter embodiment, the proximal end of the infusion fiber extending outwardly from the guide catheter can be manipulated to locate the distal end of the infusion fiber in the target area. An infusion pump is connected to the proximal end of the infusion fiber to infuse a minute quantity of fluid at an extremely low flow rate into the brain of the patient.

Abstract: Sequences are provided that are capable of directing circular adeno-associated virus replication, useful in vectors for providing therapeutic agents to a subject in need thereof. The vectors of the invention are particularly useful in the treatment of acute medical conditions requiring rapid gene expression. Further provided are methods for producing packaged defective viral vectors.

Abstract: The present invention describes a method of identifying inducible genetic regulatory sequences that can control the transcription of specific gene transcripts. Methods of using inducible genetic regulatory sequences are also discussed. In particular, the genetic regulatory sequences of the present invention can modulate the transcription of a nucleic acid transcript in vivo.

Abstract: The invention relates to a method of delivering exogenous DNA to a target cell of the mammalian central nervous system using an adeno-associated virus (AAV)-derived vector. Also included in the invention are the AAV-derived vectors containing exogenous DNA which encodes a protein or proteins which prevent or treat nervous system disease, and a method of prevent or treating such disease.

Abstract: The invention relates to a method of delivering exogenous DNA to a target cell of the mammalian central nervous system using an adeno-associated virus (AAV)-derived vector. Also included in the invention are the AAV-derived vectors containing exogenous DNA which encodes a protein or proteins which treat nervous system disease, and a method of treating such disease.

Abstract: The invention relates to the use of adeno-associated virus vectors for the transfer of genes to the heart and vasculature. The vector preferably contains a gene encoding a protein which improves heart and vascular function during heart failure. In a specific embodiment, the vector is introduced into the heart and vasculature via a catheter, with the aid of fluoroscopy. The method and vectors for use therein provide for safe and stable gene expression of the transferred genes.

Abstract: The present invention relates to a viral vector capable of the transfer and in vivo expression of growth-associated protein (B-50/GAP-43) in neuronal target cells of a mammalian host. The viral vector contains a recombinant DNA molecule comprising a B-50/GAP-43 gene operably associated with a promoter, which promoter controls short term, high level expression of the B-50/GAP-43 gene. Preferably, the viral vector is a defective viral vector, in particular a defective herpes virus or an adeno-associated virus. In a specific embodiment, defective herpesvirus, adenovirus, and adeno-associated virus viral vectors containing the rat B-50/GAP-43 gene under control of the human cytomegalovirus immediate early promoter have been prepared. The invention further provides a method for treating nerve damage in a subject. The method comprises introducing a vector comprising a B-50/GAP-43 gene operably associated with a promoter into a damaged nerve tissue of a subject.

Abstract: A replication defective DNA viral vector that comprises a gene of interest encoding a protein having a demonstrated therapeutic effect on a host cell is disclosed. The vector comprises the gene in operable linkage with a neural tissue-specific promoter, which is a promoter derived from a gene normally produced in the host cell. In particular an HSV-1 vector is used. A preferred DNA defective vector is the dvHBENK which includes a promoter prepared from the rat preproenkephalin gene, the promoter being in operable linkage with the lacZ gene. The disclosed DNA viral vector is useful for achieving stable in vivo long-term expression, in particular in mammalian brain cells.