Mannosylated poly(beta-amino esters) for targeted antigen presenting cell immune modulation

What is it about?

The manuscript describes the synthesis of a cationic polymer for targeted delivery of genetic cargo to antigen presenting cells (APCs) with the long-term objective of directing and enhancing vaccine immune responses.

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Why is it important?

Our results demonstrate potent gene delivery in both in vitro and in vivo settings. Using a combination of 96-well-based and flow cytometry forms of assessment, a new mannose-conjugated poly(beta-amino ester) demonstrated significantly improved in vitro gene delivery when compared to commercially-vetted control transfection reagents. Experiments were assessed using a new gene delivery metric termed Total Gene Delivery Performance (TGDP), which takes into account the two previously-mentioned forms of transfection experiments as well as APC cellular viability. The results support the promise of the new vector for broad subsequent gene delivery applications. However, the mannose addition was introduced to specifically target APCs in the context of genetic antigen delivery and immune response. To this end, the approach was tested in vivo using the model antigen ovalbumin. The data generated provide additional confirmation of the approach and potential of the new vector by demonstrating significantly improved immune responses when compared to genetic and protein antigen controls. Importantly, these results emphasize significant potency when normalized to genetic cargo and were obtained without the aid of adjuvant.