Described herein are CpG-adjuvanted SARS-CoV-2 vaccines and compositions and methods of producing and administering said vaccines to subjects in need thereof.

The present disclosure relates to the production of transmissible vims defective interfering particles (DIPs), particularly those of dengue virus as well as methods of their production. The DIPs have particular utility as immunogenic compositions and vaccines.

The present disclosure relates to the production of transmissible vims defective interfering particles (DIPs), particularly those of dengue virus as well as methods of their production. The DIPs have particular utility as immunogenic compositions and vaccines.

An engineered phage-derived particle (PDP) for expressing a transgene in a target cell transduced with a bacteriophage, the PDP includes (i) less than about 500 bp of DNA from the bacteriophage genome, (ii) an ITR-flanked therapeutic gene up to 20 kb, (iii) an endosomal escape sequence, (iv) a nuclear localization sequence, and (v) a cell-specific targeting moiety. The PDP may escape lysosomal degradation, traffic across the nuclear envelope and expressed a therapeutic gene in a mammalian cell.

An engineered phage-derived particle (PDP) for expressing a transgene in a target cell transduced with a bacteriophage, the PDP includes (i) less than about 500 bp of DNA from the bacteriophage genome, (ii) an ITR-flanked therapeutic gene up to 20 kb, (iii) an endosomal escape sequence, (iv) a nuclear localization sequence, and (v) a cell-specific targeting moiety. The PDP may escape lysosomal degradation, traffic across the nuclear envelope and expressed a therapeutic gene in a mammalian cell.

This disclosure provides compositions, methods, and systems comprising a papillomaviral delivery vehicle for the delivery of gene editing material to cells. The papillomaviral delivery vehicle comprises a papillomavirus-derived capsid and DNA encoding a gene editing material encapsulated by the capsid. The papillomaviral delivery vehicle can be transduced into a cell under conditions conducive for the cell to synthesize the gene editing material. The cell can comprise a polynucleotide target and the gene editing material can target the polynucleotide target. The polynucleotide target can be a DNA polynucleotide target or RNA polynucleotide target.

CRISPR RNA-guided nucleases are routinely used for sequence-specific manipulation of DNA. While CRISPR-based DNA editing has become routine, analogous methods for editing RNA have yet to be established. Here we repurpose the type III-A CRISPR RNA-guided nuclease for sequence-specific cleavage of the SARS-CoV-2 genome. The type III cleavage reaction is performed in vitro using purified viral RNA, resulting in sequence-specific excision of 6, 12, 18 or 24 nucleotides. Ligation of the cleavage products is facilitated by a DNA splint that bridges the excision and RNA ligase is used to link the RNA products before transfection into mammalian cells. The SARS-CoV-2 RNA is infectious and standard plaque assays are used to recover viral clones. Collectively, this work demonstrates how type III CRISPR systems can be repurposed for sequence-specific editing of RNA viruses including SARS-CoV-2 and more generally for gene therapy.

CRISPR RNA-guided nucleases are routinely used for sequence-specific manipulation of DNA. While CRISPR-based DNA editing has become routine, analogous methods for editing RNA have yet to be established. Here we repurpose the type III-A CRISPR RNA-guided nuclease for sequence-specific cleavage of the SARS-CoV-2 genome. The type III cleavage reaction is performed in vitro using purified viral RNA, resulting in sequence-specific excision of 6, 12, 18 or 24 nucleotides. Ligation of the cleavage products is facilitated by a DNA splint that bridges the excision and RNA ligase is used to link the RNA products before transfection into mammalian cells. The SARS-CoV-2 RNA is infectious and standard plaque assays are used to recover viral clones. Collectively, this work demonstrates how type III CRISPR systems can be repurposed for sequence-specific editing of RNA viruses including SARS-CoV-2 and more generally for gene therapy.

Provided herein is a recombinant AAV (rAAV) comprising an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5′ inverted terminal repeat (ITR), an engineered nucleic acid sequence encoding a functional hSGSH, a regulatory sequence which direct expression of hSGSH in a target cell, and an AAV 3′ ITR. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treating a human subject diagnosed with MPS IIIA.

Provided herein is a recombinant AAV (rAAV) comprising an AAV capsid and a vector genome packaged therein, wherein the vector genome comprises an AAV 5′ inverted terminal repeat (ITR), an engineered nucleic acid sequence encoding a functional hSGSH, a regulatory sequence which direct expression of hSGSH in a target cell, and an AAV 3′ ITR. Also provided is a pharmaceutical composition comprising a rAAV as described herein in a formulation buffer, and a method of treating a human subject diagnosed with MPS IIIA.