Laborataory of Macromolecule Drug Delivery
LiujiaAssistant Professor , PhD, Assistant Professor
Research Direction: understanding the mechanisms of cellular uptake of macromolecules and via this process developing next-generation macromolecule drug delivery technologies.
1. Dissection of mechanisms of macromolecule internalization. In order to understand the key molecules mediating the internalization of macromolecules, we constructed focused CRISPR/Cas9 sgRNA library targeting to surface protein (surfaceome library). Compared with genome-wide CRISPR sgRNA library, the surfaceome library does not contain gene targets that may interfere with the screen process (tumor suppressor genes etc.), thereby dramatically increasing the screening efficiency. Using this library, we have successfully identified host surface proteins that mediated Zika virus infection. We plan to use these focused libraries to understand the internalization mechanisms of macromolecules such as exosome and toxic proteins.
2. Precision genome editing using anti-CRISPR peptides and small molecules. CRISPR/Cas9 is often associated with unwanted “off-target” gene editing. One major cause of these “off-target” activity is the accumulated Cas9 nuclease and sgRNA inside cells. Inhibition of the excess CRISPR/Cas9 activity can be a feasible route for improving the genome editing fidelity. Using our house-made EGFP reporter cell line, we have identified lead peptides and small molecules that can suppress CRISPR/Cas9 activity.
3. Zinc finger protein (ZFP)-mediated macromolecule delivery system. Zinc finger protein is the most abundant transcription factors in human. From our previous studies, we have discovered that ZFP can be used as an efficient delivery tool to transport macromolecule cargos such as proteins and nucleic acids into mammalian cells. We have demonstrated that ZFP can mediate efficient delivery of botulinum neurotoxins, superoxide dismutase and targeted nucleases. These delivery technologies have been patented and licensed to biotech startup companies.
Dr Liu's group has established CRISPR surfaceome library-based functional genomics screening platform for understanding of the internalization mechanisms of macromolecules. Through previous work, Dr Liu's group has constructed two generations of CRISPR surfaceome libraries for screening in human cells and has validated the efficiency of these libraries in multiple screening models. Using surfaceome CRISPR screen, Dr Liu has identified the host factors for a variety of pathogens including Zika virus, rhinovirus and SARS-CoV-2. This work has been published on high profile journals including Nat Microbiol. Meanwhile, Dr Liu has discovered a series of small-molecule and peptidyl CRISPR inhibitors for precison genome engineering. This work has been published on high profile journals including Angew Chem Int Ed, Nat Protoc, CSH Persp Biol. In addition, Dr Liu has established zinc finger protein-based drug delivery platform, which is highly appreciated in drug development field and achieved 1.8 million USD technology transfer.
Representative Publications (*First Author, # Corresponding Author)
Volume Editor. Zinc Finger Proteins: Methods and Protocols. Methods in Molecular Biology. 2018. Humana Press.
Group Member and Photo