Abstract: The present disclosure is in the field of genome engineering, particularly targeted integration of anti-HIV transgenes into the genome of a cell for the treatment and/or prevention of HIV.

Abstract: Disclosed herein are compositions and methods for generating chromosomal translocations and targeted deletions of specific lengths and at specific locations the genome of cell.

Abstract: Disclosed herein are methods and compositions for generating a single-stranded break in a target sequence, which facilitates targeted integration of one or more exogenous sequences.

Abstract: Disclosed herein are methods and compositions for modulating activity of CXCR4 genes, for example using zinc finger transcription factors (ZF-TFs) or zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding ZF-TFs or ZFNs, vectors comprising polynucleotides encoding ZF-TFs or ZFNs and cells comprising polynucleotides encoding ZF-TFs or ZFNs and/or cells comprising ZF-TF or ZFNs are also provided.

Abstract: Viral infection is a persistent cause of human disease. Guided nuclease systems of the invention target the genomes of viral infections, rendering the viruses incapacitated. The invention further provides delivery methods and compositions for antiviral therapeutics. Methods and compositions are provided for targeted delivery of antiviral therapeutics into cells of interest using, for example, viral vectors such as adenovirus, AAV, and replication incompetent HSV. These and other delivery systems can be used as vehicles to deliver DNA vectors encoding a nuclease or a cell-killing gene. These delivery methods can also be used to deliver naked DNA or RNA, protein products, plasmids containing a promoter that is active only in a latent viral state which drives a cell-killing gene, or other therapeutic agents.

Abstract: Disclosed herein are methods and compositions for generating a single-stranded break in a target sequence, which facilitates targeted integration of one or more exogenous sequences.

Abstract: Disclosed herein are methods and compositions for inhibiting viral entry into cells.

Abstract: The invention relates to systems and methods for removing viral genetic sequences from host genomes by using a computer system to read a nucleotide string next to a protospacer adjacent motif (PAM) in the viral sequence, determine that the host genome lacks any region that matches the nucleotide string according to a predetermined similarity criteria and is adjacent to the PAM, and provide a guide sequence at least partially complementary to the nucleotide string. Providing the guide sequence may include synthesizing a guide RNA that includes a portion that is complementary to the nucleotide string.

Abstract: The invention relates to methods for treating cytomegalovirus (CMV) in cells and tissues using targeted nucleases. The nucleases may be CRISPR/Cas9 complexes with guided RNA to target and inactivate CMV genomes within cells and tissues. The nucleases degrade or destroy the CMV genomes within the cells and tissues. Methods of the invention can be used to treat tissues, such as whole organs, prior to transplantation.

Abstract: The invention relates to methods for generating viral-free cells using nucleases for use in transplantation. The nucleases may be CRISPR/Cas9 complexes with guided RNA to target and inactivate viral genomes within cells. The nucleases degrade or destroy the viruses within the cells prior to transplantation.

Abstract: The invention provides compositions and methods for treating human papillomavirus (HPV) infections using a targetable nuclease, which compositions and methods can be used to selectively target the HPV genome or selectively express the targetable nuclease within cells that infected by HPV. By selectively targeting cells infected by HPV, the HPV genome within infected cells, or both, the nuclease is able to cleave the HPV genome thereby inactivating it and rendering it inoperable, interfering with the virus's ability to propagate even where the virus is in a latent stage of infection. Since latent HPV can be cleaved and eradicated from the host cells, compositions and methods of the invention may be used to treat HPV infections and potentially prevent many of the adverse health consequences associated with the papillomavirus.

Abstract: Herpes simplex virus (HSV) including herpes simplex virus 1 and 2 (HSV-1 and HSV-2) are a persistent cause of human disease with no known cure. Guided nuclease systems target specific regions of the HSV-1 and HSV-2 genomes, disrupting the virus' nucleic acid and rendering even latent viruses incapacitated.

Abstract: A load-store collision detection system for a speculative out of order processing engine which includes a scheduler that dispatches instructions to multiple instruction pipelines. The instruction pipelines include a load pipeline that provides a load valid signal when a speculatively dispatched load instruction is executing. The load-store collision detection system includes comparator logic, broadcast logic, and kill logic. The comparator logic asserts a clear signal when a virtual address of the speculatively dispatched load instruction matches at least one store instruction virtual address of a previously dispatched store instruction whose corresponding store data is not ready yet. The broadcast logic broadcasts the load valid signal to the scheduler to enable dispatch of any instructions dependent upon the speculatively dispatched load instruction. The kill logic invalidates the load valid signal when the clear signal is asserted to avoid a load-store collision that reduces processing performance.

Abstract: Viral infection is a persistent cause of human disease. Guided nuclease systems target the genomes of viral infections, rendering the viruses incapacitated.

Abstract: Methods are provided for diagnosis and prognosis of disease by analyzing expression of a set of genes obtained from single cell analysis. Classification allows optimization of treatment, and determination of whether on whether to proceed with a specific therapy, and how to optimize dose, choice of treatment, and the like. Single cell analysis also provides for the identification and development of therapies which target mutations and/or pathways in disease-state cells.

Abstract: The invention provides methods and compositions that remove target genetic material from a subject by hydrodynamic delivery of an enzyme that degrades the target genetic material. The methods include delivering a solution include a nucleic acid, protein, or ribonucleoprotein to a blood vessel at a pressure sufficient to cause the material to enter cells proximal to the blood vessel. The enzyme may be Cas9 and may be provided with a guide RNA. The target genetic material may be viral genome with the guide RNA complementary to a portion of the viral genome.

Abstract: A reissue instruction parking system for a microprocessor including a reservation stations module that dispatches instructions for execution and a reorder buffer that reissues instructions to the reservation stations module during a reissue state, in which the reissue instruction parking system includes at least one first pipeline stage and at least one second pipeline stage, in which the first pipeline stages provide a first reissue instruction from a reissue data path to the reservation stations module during the reissue state and that parks the first reissue instruction once the reservation stations module is determined to be full, and in which the second pipeline stages select a pointer to the reorder buffer which provides a corresponding first reissue instruction onto the reissue data path, in which the second pipeline stages are placed into a hold state when a second full signal is asserted.

Abstract: A parallelized multiple dispatch ordered queue including an ordered queue, qualify logic, ordered select logic, and dispatch logic. The ordered queue stores candidates in order from oldest to youngest into multiple entries. The ordered queue is divided into N groups in which an i'th group includes every i'th entry of every N entries of the ordered queue, wherein i is an integer less than or equal to N. The qualify logic determines whether any candidate is ready to be dispatched. The ordered select logic respectively determines the oldest candidate in each group that is ready to be dispatched. The dispatch logic dispatches the oldest ready candidates in parallel. The shift logic shifts the stored candidates in the ordered queue to fill any vacant entries between remaining ones of the stored candidates without changing an order of the remaining ones of the stored candidates in the ordered queue. The ordered queue may have any size or depth and N is any suitable integer determining the number of candidates (e.g.

Abstract: Disclosed herein are compositions and methods for generating chromosomal translocations and targeted deletions of specific lengths and at specific locations the genome of cell.

Abstract: Methods are provided for diagnosis and prognosis of disease by analyzing expression of a set of genes obtained from single cell analysis. Classification allows optimization of treatment, and determination of whether on whether to proceed with a specific therapy, and how to optimize dose, choice of treatment, and the like. Single cell analysis also provides for the identification and development of therapies which target mutations and/or pathways in disease-state cells.