Compositions that specifically cleave target sequences in Herpesviridae, for example Varicella zoster virus (VZV) include nucleic acids encoding a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) associated endonuclease and a guide RNA sequence complementary to a target sequence in VZV. These compositions are administered to a subject for treating an infection or at risk for contracting a VZV infection.

Provided herein are CasX:gNA systems comprising CasX polypeptides, guide nucleic acids (gNA), and optionally donor template nucleic acids useful in the modification of a SOD1 gene. The systems are also useful for introduction into cells, for example eukaryotic cells having mutations in the SOD1 protein or the SOD1 regulatory element. Also provided are methods of using such CasX:gNA systems to modify cells having such mutations and utility in methods of treatment of a subject with a SOD1-related disease.

The present invention discloses the use of placenta permeable small RNAs, particularly the use of small ribonucleic acids (small RNAs) in the preparation of a medicament comprising the small RNAs as active substances, wherein the medicament is administered to a mother's body directly and the small RNAs enter the fetus through the placenta to play their role in the fetus. Trials have shown that the small RNAs when administered directly to the mother's body in different ways such as oral and intragastric administration can enter the fetus through the placenta to play their role directly in the fetus. The invention provides a novel administration method that can minimize the damage to a fetus.

Methods and compositions treat a viral infection use a nuclease and an inhibitor that prevents DNA repair, such as a CRISPR-associated nuclease and a small molecule that inhibits an enzyme of a repair pathway. Under guidance of a targeting sequence, the nuclease cuts viral nucleic acid without cutting the patient's genome. The cut ends of the viral nucleic acid are not repaired because the inhibitor prevents a repair mechanism.

Compositions and methods for treating infection-associated cancer include the use of a nuclease that cuts nucleic acid of an oncovirus in combination with an adjunct chemotherapeutic that treats cancerous cells. For example, a Cas9 endonuclease and a guide RNA that matches a target in a viral genome without having any corresponding match in the human genome can be delivered along with an anti-apoptotic inhibitor.

The present disclosure relates to recombinant viral vectors for the treatment and prevention of cancer. Oncolytic viral vectors incorporate one or more of the following features: viral replication restriction by insertion of tumor-suppressive microRNA (miRNA) target sequences into the viral genome; disruption of oncogenic miRNA function; cancer microenvironment remodeling; and cancer cell targeting by incorporation of protease-activated antibodies into the viral particle.

The present disclosure provides compositions and methods for inhibiting herpesvirus replication in a cell infected with herpesvirus. The composition includes a double stranded DNA molecule including a sequence of a cis regulatory sequence (crs) of a herpesvirus, wherein the crs is flanked on the 5′ end by a first sequence of at least 2 base pairs and on the 3′ end by a second sequence of at least 2 base pairs.

Aspects of the application relate to methods and compositions for delivering therapeutic nucleic acids to neural cells or tissue in a subject. Additional aspects of the application relate to therapeutic nucleic acids, for example therapeutic ribozymes, that are useful for inhibiting viral reactivation in a subject.

Amyloid precursor protein (APP) dysfunction is a key feature in Alzheimer's disease (AD). The sortilin-related receptor 1 (SORLA) functions as a chaperone protein to APP and has reduced expression in AD brains. The APP and SORLA dysfunction results in homeostasis destabilization. Herpesviruses are suspected to be involved in AD pathogenesis. Using a strategic nucleotide BLAST to query SORL1 and APP nucleotide alignment on all Herpesviridae genomes identified similarity sequences from the Epstein-Barr virus and herpes simplex virus 2. The invention describes a treatment to alleviate EBV and HSV2-mediated neurodegeneration by delivering antisense oligonucleotides sequences that target the EBV and HSV2 non-coding sequences to block SORLA and APP disruption. The invention further describes methods to eradicate EBV infection by delivering inducible expression of antisense oligonucleotides targeting EBV genes or an inducible CRISPR/Cas gene-editing system, together with an expression construct encoding anti-apoptotic proteins or with anti-apoptotic proteins for the prevention of cell-mediated apoptosis.

The present disclosure relates to compositions, systems, vectors, and methods for the treatment, prevention, and/or reduction of viral infection and viral infection-related diseases. In particular, the methods disclosed herein involve gene editing approaches using a genome editing system targeting a viral genome, where the expression of at least one component of the gene editing system is regulated by a promoter derived from the targeted viral family, genus, and/or species.