Research & Pipeline


Intelligent Screening and Customized Deliverying Platform for Delivery System

The existing cellular screening platform cannot accurately characterize the expression of LNPs in vivo. Therefore, we innovatively applied the in vivo barcoding technology. More specifically, after in vivo delivering the pre-mixed individually-designed LNPs, we can efficiently screen their profiles of targets at tissue and cell level by high throughput sequencing of DNA barcodes that are unique to each single LNP.

Precise Separation of Protein Coronas Based on Affinity Chromatography

Lipid nanocarriers absorb endogenous macromolecules (proteins, lipids, etc.) in blood, interstitial fluids or cytoplasm to form "protein coronas" in vivo. It is a challenging task to accurately resolve the structural and functional feature of the protein coronas. Centrifugation and size exclusion chromatography are common methods to separate protein coronas, but problems like low collection efficiency and impurity still exist.

To achieve accurate and efficient separation of protein coronas on PEG-encapsulated liposomes (sLip), we developed an affinity chromatography (AfC) technique based on anti-PEG single-stranded variable fragments (PEG-scFv) (Chu et al., Zhan*. Nano Lett, 2021). AfC elevates the collection efficiency by 43 times compared to centrifugation. In addition, this method avoids the contamination of endogenous vesicles and protein aggregates that occur during centrifugation, thereby retaining loosely bound proteins. Overall, our Afc technique provides a new method for in-depth interpretation of protein coronas.

A Customized Delivery Platform based on the MoA between mRNA-LNP and Target Organ

On the basis of abovementioned breakthrough, we soon developed a brain-targeting delivery system by manipulating the protein corona’s function (Zhang et al.,Zhan*, Nat Commun, 2019). Specifically, we first modified liposomes with a short peptide(SP-SLIP). After entering the bloodstream, SP-SLIP is associated with brain-targeting apolipoproteins (ApoE\ApoJ\ApoA1) through interactions between the postganglionic domains of SP and apolipoproteins. Meanwhile, the function of absorbed plasma ApoE is preserved. This discovery paves a new way to promote clinical transformation of targeted drug delivery systems.

This customized delivery platform regulates key plasma proteins on the surface of lipid nanocarriers to achieve targeted tissue/cell drug delivery mediated by protein crowns. We will also use this platform to fuel further exploitation of mRNA-LNP targeted delivery.

Continuous Smart Manufacturing Platform

Our team invented a continuous smart manufacturing platform for the preparation of new LNPs. Different from the existing ones, this platform can continuously manipulate the concentration of single or multiple lipid components in LNP formualtion. Our platform unleashes the existing patent restriction, and allows the production of LNPs with diverse in vivo characteristics to meet different clinical scenarios.

Precise Drug Administration Platform

Based on the biomarker for in vivo performance of mRNA-LNP
济南控制系统工程 | 武汉生物制药 | 电力测试 |