RT Journal Article
SR Electronic
T1 Engineering the Immune Adaptor Protein STING as a Biologic
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.02.18.431824
DO 10.1101/2021.02.18.431824
A1 Xin Sun
A1 Yun Ni
A1 Yanpu He
A1 Mengdi Yang
A1 Tetsuo Tani
A1 Shunsuke Kitajima
A1 David A. Barbie
A1 Jiahe Li
YR 2021
UL http://biorxiv.org/content/early/2021/03/22/2021.02.18.431824.abstract
AB Activation of the stimulator of interferon genes (STING) pathway through cyclic dinucleotides (CDNs) has been explored extensively as potent vaccine adjuvants against infectious diseases as well as to increase tumor immunogenicity towards cancer immunotherapy in solid tumors. Over the last decade, a myriad of synthetic vehicles, including liposomes, polymers, and other nanoparticle platforms, have been developed to improve the bioavailability and therapeutic efficacy of STING agonists in preclinical mouse models. In comparison to synthetic materials, protein-based carriers represent an attractive delivery platform owing to their biocompatibility, amenability to genetic engineering, and intrinsic capacity to form well-defined structures. In the present work, we have engineered the immune adaptor STING as a protein-based delivery system for efficient encapsulation and intracellular delivery of CDNs. Through genetic fusion with a protein transduction domain, the recombinant STING can spontaneously penetrate cells to markedly enhance the delivery of CDNs in a mouse vaccination model and a syngeneic mouse melanoma model. Moreover, motivated by recent findings that certain tumor cells can evade immune surveillance via loss of STING expression, we further unveiled that our STING platform can serve as a functional vehicle to restore the STING signaling in a panel of lung and melanoma cell lines with impaired STING expression. Taken together, our STING-based protein delivery platform may offer a unique direction towards targeting STING-silenced tumors as well as augmenting the efficacy of STING-based vaccine adjuvants.Competing Interest StatementThe authors have declared no competing interest.