Vector Strategies to Actualize B Cell-Based Gene Therapies

J Immunol. 2021 Aug 1;207(3):755-764. doi: 10.4049/jimmunol.2100340.


Recent developments in genome editing and delivery systems have opened new possibilities for B cell gene therapy. CRISPR-Cas9 nucleases have been used to introduce transgenes into B cell genomes for subsequent secretion of exogenous therapeutic proteins from plasma cells and to program novel B cell Ag receptor specificities, allowing for the generation of desirable Ab responses that cannot normally be elicited in animal models. Genome modification of B cells or their progenitor, hematopoietic stem cells, could potentially substitute Ab or protein replacement therapies that require multiple injections over the long term. To date, B cell editing using CRISPR-Cas9 has been solely employed in preclinical studies, in which cells are edited ex vivo. In this review, we discuss current B cell engineering efforts and strategies for the eventual safe and economical adoption of modified B cells into the clinic, including in vivo viral delivery of editing reagents to B cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies / genetics
  • Antibodies / metabolism
  • B-Lymphocytes / physiology*
  • CRISPR-Cas Systems
  • Epitopes
  • Genetic Engineering
  • Genetic Therapy / trends*
  • Humans
  • Immunotherapy
  • Receptors, Antigen, B-Cell / genetics*


  • Antibodies
  • Epitopes
  • Receptors, Antigen, B-Cell