B Lymphocyte Protein Factories produced by Hematopoietic Stem Cell Gene Editing

Area of Science:

• Gene editing and cell therapy
• Immunology and infectious disease

Background:

• Challenges exist in long-term in vivo production of therapeutic proteins and vaccines for broad protection against pathogens.
• Current methods struggle to achieve sustained, high-level expression of antibodies or therapeutic proteins.

Purpose of the Study:

• To develop an alternative gene-editing strategy for sustained, high-level antibody and therapeutic protein production.
• To engineer hematopoietic stem and progenitor cells (HSPCs) for long-term expression of therapeutic proteins and antibodies.

Main Methods:

• Utilized gene editing on a small number of hematopoietic stem and progenitor cells (HSPCs).
• Edited HSPCs were directed to produce antibody or cargo protein-synthesizing B lymphocytes.
• Demonstrated antigen-specific activation, clonal expansion, and differentiation into plasma cells.

Main Results:

• Achieved long-term, high-level serum antibody production against HIV-1 and malaria.
• Developed broadly neutralizing antibodies (bNAbs) against influenza virus, conferring universal protection.
• Engineered B cells functioned as self-amplifying protein factories for therapeutic purposes.

Conclusions:

• Presents a novel gene-editing paradigm for cell therapy.
• This approach enables sustainable production of therapeutic antibodies and proteins via engineered B cells.
• Offers a promising strategy for preventing and treating infectious diseases.