DNA-Directed Assembly of Multivalent Lipid Nanoparticles for Targeted T Cell Gene Delivery.

Area of Science:

• Biotechnology
• Immunology
• Gene Therapy

Background:

• Lipid nanoparticles (LNPs) are crucial for in vivo T cell engineering, facing challenges in precise targeting and efficient mRNA translation.
• While single-targeted LNPs are studied, bispecific LNPs offer enhanced delivery and targeting by engaging multiple T cell receptors.

Purpose of the Study:

• To develop a rapid method for assembling and evaluating bispecific LNPs for targeted mRNA delivery to T cells.
• To compare the efficacy of bispecific LNPs against monotargeted LNPs for in vitro and in vivo applications.

Main Methods:

• Utilized a DNA-tethering strategy for rapid modification of LNPs with commercial antibodies.
• Evaluated various bispecific LNP formulations for targeted mRNA delivery and T cell transfection in vitro and in vivo.

Main Results:

• Bispecific LNPs demonstrated improved T cell targeting and transfection efficiency compared to monotargeted LNPs.
• Targeting molecules influenced LNP biodistribution, affecting spleen and liver accumulation.
• The DNA-tethering method enabled efficient screening of antibody combinations for targeted gene delivery.

Conclusions:

• Bispecific LNPs represent a promising advancement for enhancing in vivo gene delivery to T cells.
• The developed DNA-tethering approach facilitates high-throughput screening for optimizing antibody-targeted LNPs.
• This modular strategy can be customized for developing novel therapeutics for various diseases.