The present disclosure describes the generation and the use of Ad variants (Ad) possessing any combination of mutations in genes that code for the hexon, penton, fiber, and non-structural proteins, where simultaneous modification of hexon and penton are made to avoid the trapping of Ad in the liver and to reduce toxicity after intravascular virus administration. Such liver de-targeted Ad can be useful tool for selective and specific gene delivery to extra-hepatic tissues and cells, including disseminated metastatic cancer cells.

The present disclosure describes the generation and the use of Ad variants (Ad) possessing any combination of mutations in genes that code for the hexon, penton, fiber, and non-structural proteins, where simultaneous modification of hexon and penton are made to avoid the trapping of Ad in the liver and to reduce toxicity after intravascular virus administration. Such liver de-targeted Ad can be useful tool for selective and specific gene delivery to extra-hepatic tissues and cells, including disseminated metastatic cancer cells.

Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of retinal cells as compared to the infectivity of the retinal cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more ceils of the retina for the treatment of retinal disorders and diseases.

Provided herein are variant adeno-associated virus (AAV) capsid proteins having one or more modifications in amino acid sequence relative to a parental AAV capsid protein, which, when present in an AAV virion, confer increased infectivity of one or more types of retinal cells as compared to the infectivity of the retinal cells by an AAV virion comprising the unmodified parental AAV capsid protein. Also provided are recombinant AAV virions and pharmaceutical compositions thereof comprising a variant AAV capsid protein as described herein, methods of making these rAAV capsid proteins and virions, and methods for using these rAAV capsid proteins and virions in research and clinical practice, for example in, e.g., the delivery of nucleic acid sequences to one or more ceils of the retina for the treatment of retinal disorders and diseases.

Insecticidal toxins described herein are fused toxin peptides made up of a targeting domain fused to a toxin domain. The targeting peptide generates a specific association with mosquitoes by causing the fused toxin peptide to bind mosquitoes in a way that leads to the insecticidal activity. Transgenic plants described herein are mosquitocidal by expressing an insecticidal toxin protein in nectar that includes a targeting peptide to ensure specificity against mosquitoes. These transgenic plants serve as role models for safety, since they are non-crop plants and specific to one mosquito species.

Insecticidal toxins described herein are fused toxin peptides made up of a targeting domain fused to a toxin domain. The targeting peptide generates a specific association with mosquitoes by causing the fused toxin peptide to bind mosquitoes in a way that leads to the insecticidal activity. Transgenic plants described herein are mosquitocidal by expressing an insecticidal toxin protein in nectar that includes a targeting peptide to ensure specificity against mosquitoes. These transgenic plants serve as role models for safety, since they are non-crop plants and specific to one mosquito species.

Betacoronavirus Spike proteins, or fragments thereof, including substitution mutations designed to increase stability, decrease the risk of antibody dependent enhancement, or both; and that are useful in, for example, immunogenic compositions.

A method for producing genetically engineered immune cells, e.g. T cells, or iPSCs which uses an RNA-scaffold mediated base editing system. The method enables precise modifications to be made to the genome whilst minimizing the possibility of off-target effects, making the method particularly suitable for therapeutic applications.

Compositions and methods are presented that allow for detection and prediction of an immune response in a subject that is selected to receive or that has received a vaccine. In selected embodiments, whole blood is used as starting material to obtain both dendritic cells and T cells, and synthetic or recombinant polypeptide(s) are used that include an antigen of the vaccine. The dendritic cells are then exposed to the synthetic or recombinant polypeptide(s), and thusly exposed dendritic cells are combined with the T cells to generate antigen reactive T cells. For detection or quantification, the antigen reactive T cells are expanded in vitro prior to ELISPOT or FACS analysis. Advantageously, such systems and methods are especially suitable for ascertaining an immune response against cancer antigens following vaccination with an anti-cancer vaccine.

The present disclosure relates to recombinant human adenoviruses engineered to express a structural protein of a coronavirus. The recombinant adenoviruses are suitable for active immunization against a coronavirus in a human subject. Additionally, immune globulin obtained from immunized human subjects is suitable for passive immunization of a coronavirus-infected human subject.