Ontology highlight
ABSTRACT:
PROVIDER: PRJNA665932 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12736900.fastq.gz | Fastqsanger.gz | |||
| SRR12737000.fastq.gz | Fastqsanger.gz | |||
| SRR12737100.fastq.gz | Fastqsanger.gz | |||
| SRR12737200.fastq.gz | Fastqsanger.gz | |||
| SRR12737300.fastq.gz | Fastqsanger.gz |
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Project description:Somatic hypermutation (SHM) drives antibody affinity maturation in B cells, and mimicking this process has advanced therapeutic antibody development. Unlike conventional base editing, antibody diversification requires diverse mutations within the antibody complementary determining region (CDR) loops. Here, we engineered a hyper-antibody editor, HAE1, by integrating cytosine and adenine deaminases with a nicked, PAMless Cas9 variant, SpRY. HAE1 enables broad-spectrum mutagenesis with unrestricted targeting, fully covering mutation types observed in nature. Moreover, we developed a dual-expression system in mammalian cells that allows simultaneous expression of both transmembrane and secreted full-length antibodies, streamlining mutation, selection, and validation within the same cells. Using this platform, we rejuvenated the SARS-CoV-2 antibody CV07-209, restoring potency against Omicron variants. These results demonstrate the effectiveness of HAE1 as a powerful tool for antibody engineering, offering a practical strategy for evolving antibodies to address rapidly mutating pathogens and other therapeutic challenges.
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Project description:The use of CRISPR/Cas proteins for the creation of multiplex genome-engineering represents an important avenue for crop improvement, and further improvements for creation of knock-in plant lines via CRISPR-based technologies may enable the high-throughput creation of designer alleles. To circumvent limitations of the commonly used CRISPR/Cas9 system for multiplex genome-engineering, we explored the use of Moraxella bovoculi 3 Cas12a (Mb3Cas12a) for multiplex genome-editing in Arabidopsis thaliana. We identified optimized promoter sequences for driving expression of single transcript multiplex crRNA arrays in A. thaliana, resulting in stable germline transmission of Mb3Cas12a-edited alleles at multiple target sites. By utilizing this system, we demonstrate single-transcript multiplexed genome-engineering using of up to 13 crRNA targets. We further show high target specificity of Mb3Cas12a-based genome-editing via whole-genome sequencing. Taken together, our method provides a simplified platform for efficient multiplex-genome-engineering in plant-based systems.
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