Related Experiment Video
Updated: Jan 9, 2026
Non-Viral Engineering of Primary Human T Cells via Homology-Mediated End-Joining Targeted Integration of Large DNA Templates
Published on: May 9, 2025
Surface-Engineered Lentiviral Vectors for Selective Gene Transfer into Subtypes of Lymphocytes
Annika M Frank1, Christian J Buchholz1,2
1Division of Medical Biotechnology, Paul-Ehrlich-Institut, 63225 Langen, Germany.
Abstract:
Lymphocytes have always been among the prime targets in gene therapy, even more so since chimeric antigen receptor (CAR) T cells have reached the clinic. However, other gene therapeutic approaches hold great promise as well. The first part of this review provides an overview of current strategies in lymphocyte gene therapy. The second part highlights the importance of precise gene delivery into B and T cells as well as distinct subtypes of lymphocytes. This can be achieved with lentiviral vectors (LVs) pseudotyped with engineered glycoproteins recognizing lymphocyte surface markers as entry receptors. Different strategies for envelope glycoprotein engineering and selection of the targeting ligand are discussed. With a CD8-targeted LV that was recently used to achieve proof of principle for the in vivo reprogramming of CAR T cells, these vectors are becoming a key tool to genetically engineer lymphocytes directly in vivo.
Insights
Gene therapy targets lymphocytes, including chimeric antigen receptor (CAR) T cells. Lentiviral vectors (LVs) engineered to target lymphocyte surface markers enable precise gene delivery for in vivo genetic engineering.
Area of Science:
- Immunology
- Gene Therapy
- Molecular Biology
Background:
- Lymphocytes are key targets for gene therapy, especially with the clinical success of chimeric antigen receptor (CAR) T cells.
- Gene therapy offers promising alternative approaches beyond CAR T cells for treating various conditions.
Purpose of the Study:
- To review current lymphocyte gene therapy strategies.
- To highlight the necessity of precise gene delivery into specific lymphocyte subtypes.
- To introduce lentiviral vectors (LVs) engineered for targeted lymphocyte gene modification.
Main Methods:
- Overview of existing gene therapy strategies for lymphocytes.
- Discussion of lentiviral vector (LV) pseudotyping with engineered glycoproteins.
- Exploration of strategies for glycoprotein engineering and ligand selection for targeting lymphocyte surface markers.
Main Results:
- Lentiviral vectors (LVs) pseudotyped with engineered glycoproteins can achieve precise gene delivery into B cells, T cells, and other lymphocyte subtypes.
- A CD8-targeted LV demonstrated proof of principle for in vivo reprogramming of CAR T cells.
- Engineered LVs are emerging as crucial tools for direct in vivo genetic engineering of lymphocytes.
Conclusions:
- Precise gene delivery into lymphocytes is critical for advanced gene therapies.
- Engineered lentiviral vectors offer a powerful platform for targeted in vivo lymphocyte gene therapy.
- These vectors represent a significant advancement in the field of genetic engineering for therapeutic applications.
