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Full-Text Articles in Medical Biotechnology
Synthetic Cationic Helical Polypeptides For The Stimulation Of Antitumour Innate Immune Pathways In Antigen-Presenting Cells, Daeyong Lee, Kristin Huntoon, Yifan Wang, Minjeong Kang, Yifei Lu, Seong Dong Jeong, Todd M Link, Thomas D Gallup, Yaqing Qie, Xuefeng Li, Shiyan Dong, Benjamin R Schrank, Adam J Grippin, Abin Antony, Jonghoon Ha, Mengyu Chang, Yi An, Liang Wang, Dadi Jiang, Jing Li, Albert C Koong, John A Tainer, Wen Jiang, Betty Y S Kim
Synthetic Cationic Helical Polypeptides For The Stimulation Of Antitumour Innate Immune Pathways In Antigen-Presenting Cells, Daeyong Lee, Kristin Huntoon, Yifan Wang, Minjeong Kang, Yifei Lu, Seong Dong Jeong, Todd M Link, Thomas D Gallup, Yaqing Qie, Xuefeng Li, Shiyan Dong, Benjamin R Schrank, Adam J Grippin, Abin Antony, Jonghoon Ha, Mengyu Chang, Yi An, Liang Wang, Dadi Jiang, Jing Li, Albert C Koong, John A Tainer, Wen Jiang, Betty Y S Kim
Faculty, Staff and Student Publications
Intracellular DNA sensors regulate innate immunity and can provide a bridge to adaptive immunogenicity. However, the activation of the sensors in antigen-presenting cells (APCs) by natural agonists such as double-stranded DNAs or cyclic nucleotides is impeded by poor intracellular delivery, serum stability, enzymatic degradation and rapid systemic clearance. Here we show that the hydrophobicity, electrostatic charge and secondary conformation of helical polypeptides can be optimized to stimulate innate immune pathways via endoplasmic reticulum stress in APCs. One of the three polypeptides that we engineered activated two major intracellular DNA-sensing pathways (cGAS-STING (for cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes) …
Engineered Protac-Cid Systems For Mammalian Inducible Gene Regulation, Dacheng Ma, Qichen Yuan, Fei Peng, Victor Paredes, Hongzhi Zeng, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Anika Patel, Megan S Liu, Zheng Sun, Xue Gao
Engineered Protac-Cid Systems For Mammalian Inducible Gene Regulation, Dacheng Ma, Qichen Yuan, Fei Peng, Victor Paredes, Hongzhi Zeng, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Anika Patel, Megan S Liu, Zheng Sun, Xue Gao
Faculty, Staff and Students Publications
Gene regulation via chemically induced dimerization (CID) is useful for biomedical research. However, the number, type, versatility, and in vivo applications of CID tools remain limited. Here, we demonstrate the development of proteolysis-targeting chimera-based scalable CID (PROTAC-CID) platforms by systematically engineering the available PROTAC systems for inducible gene regulation and gene editing. Further, we show orthogonal PROTAC-CIDs that can fine-tune gene expression at gradient levels or multiplex biological signals with different logic gating operations. Coupling the PROTAC-CID platform with genetic circuits, we achieve digitally inducible expression of DNA recombinases, base- and prime-editors for transient genome manipulation. Finally, we package a …
An Auto-Inhibited State Of Protein Kinase G And Implications For Selective Activation, Rajesh Sharma, Jeong Joo Kim, Liying Qin, Philipp Henning, Madoka Akimoto, Bryan Vanschouwen, Gundeep Kaur, Banumathi Sankaran, Kevin R Mackenzie, Giuseppe Melacini, Darren E Casteel, Friedrich W Herberg, Choel Kim
An Auto-Inhibited State Of Protein Kinase G And Implications For Selective Activation, Rajesh Sharma, Jeong Joo Kim, Liying Qin, Philipp Henning, Madoka Akimoto, Bryan Vanschouwen, Gundeep Kaur, Banumathi Sankaran, Kevin R Mackenzie, Giuseppe Melacini, Darren E Casteel, Friedrich W Herberg, Choel Kim
Faculty, Staff and Students Publications
Cyclic GMP-dependent protein kinases (PKGs) are key mediators of the nitric oxide/cyclic guanosine monophosphate (cGMP) signaling pathway that regulates biological functions as diverse as smooth muscle contraction, cardiac function, and axon guidance. Understanding how cGMP differentially triggers mammalian PKG isoforms could lead to new therapeutics that inhibit or activate PKGs, complementing drugs that target nitric oxide synthases and cyclic nucleotide phosphodiesterases in this signaling axis. Alternate splicing of PRKG1 transcripts confers distinct leucine zippers, linkers, and auto-inhibitory (AI) pseudo-substrate sequences to PKG Iα and Iβ that result in isoform-specific activation properties, but the mechanism of enzyme auto-inhibition and its alleviation …