The inventive technology relates to novel paratransgenic strategies for the biocontrol of pathogens in animal systems using interfering RNA molecules expressed in genetically modified bacteria that may be configured to colonize a target host. In one preferred embodiment, the invention includes novel paratransgenic strategies for the biocontrol of pathogens in aquatic organisms raised in aquaculture environments.

CRISPR-based gene-drive system for inhibiting antibiotic resistance of bacteria, including Escherichia coli that efficiently copies a gRNA cassette and adjacent cargo that are flanked with sequences homologous to the targeted gRNA/Cas9 cleavage site. This “pro-active” genetic system (Pro-AG) functionally inactivates an antibiotic resistance marker on a high copy number plasmid with greater efficiency than control CRISPR-based methods. Pro-AG can effectively edit large plasmids or single-copy genomic targets, or introduce functional genes, with numerous applications to biotechnology and biomedicine.

Provided herein are processes for preparing an oligomer (e.g., a morpholino oligomer). The synthetic processes described herein may be advantageous to scaling up oligomer synthesis while maintaining overall yield and purity of a synthesized oligomer.

Provided herein are processes for preparing an oligomer (e.g., a morpholino oligomer). The synthetic processes described herein may be advantageous to scaling up oligomer synthesis while maintaining overall yield and purity of a synthesized oligomer.

A red blood cell extracellular vesicle (RBCEV) loaded with a nucleic acid cargo; method for preparing the loaded vesicle; and the therapeutic use of the vesicle thereof are disclosed. The nucleic acid cargoes may be DNA or RNA, single stranded or double stranded, as well as linear or circular.

The disclosure is directed to dual variable domain immunoglobulin double-stranded RNA conjugates that are advantageous for inhibition of target gene expression, as well as compositions suitable for therapeutic use. The dual variable domain immunoglobulin comprises a first variable domain that binds to a binding target, and a second variable domain that comprises a reactive residue, where the linker is covalently conjugated to the reactive residue. The dsRNA is linked to the linker and is capable of inhibiting the expression of the target gene by RNA interference. The disclosure also provides pharmaceutical compositions comprising these conjugate and methods of inhibiting the expression of a target gene by administering these conjugates, e.g., for the treatment of various disease conditions.

The disclosure is directed to dual variable domain immunoglobulin double-stranded RNA conjugates that are advantageous for inhibition of target gene expression, as well as compositions suitable for therapeutic use. The dual variable domain immunoglobulin comprises a first variable domain that binds to a binding target, and a second variable domain that comprises a reactive residue, where the linker is covalently conjugated to the reactive residue. The dsRNA is linked to the linker and is capable of inhibiting the expression of the target gene by RNA interference. The disclosure also provides pharmaceutical compositions comprising these conjugate and methods of inhibiting the expression of a target gene by administering these conjugates, e.g., for the treatment of various disease conditions.

Disclosed are cells that have stably integrated into their genomes exogenous nucleic acid sequences, such as transgenes, within or proximal to the integration site of a sequence comprising at least part of an endogenous retrovirus (ERV) or a LTR-retrotransposon (LTR-RT), or instead of a sequence encompassing an ERV or a LTR-RT that is part or was part of the genome of the cell, as well as method of producing and using such cells. Advantageously, a high level and/or stable production of the transgene expression product(s) can be achieved. Transgene integration and expression may be furthered by modulating the DNA repair pathways of the cell, e.g., by transiently expressing a gene encoding a protein that forms part of a DNA repair pathway during transgene integration.

The invention relates to logic-gate-based Type II or Type V CRISPR-Cas constructs and methods for modifying gene expression using the CRISPR-Cas constructs and CRISPR-Cas effector proteins.

The invention relates to logic-gate-based Type II or Type V CRISPR-Cas constructs and methods for modifying gene expression using the CRISPR-Cas constructs and CRISPR-Cas effector proteins.