The transduction of the virus guided by the orthogonal chemical lysis of the sugar metabolism organism enhances the T-cell engineering transformation.

Recently, the nanomedicine research team led by Cai Lintao, a researcher at the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences, made a new breakthrough in the transformation of T-cell engineering guided by nanotechnology, and the relevant paper ,Glyco bioorthogon chemically guided virus transduction enhances T-cell engineering transformation (Glyco bioorthogon chemistal transformation) Online published online in Advanced Functional Materials, 2019, DOI: 10.1002/adfm.201807528).
Cai Lintao and his team members Pan Hong, Jin Yan and Heng Ruiyuan Zheng (Shenzhen) Biotech Co., Ltd. on the basis of the team's preliminary work (Small, 2019, 15, 1804383; Biomaterials, 2018, 181,199; Small, 2017, 13, 1604036; ACS, Nano, 2014, 8, 5468/CN 2017/093870), using cell sugar metabolism engineering to embed chemical reporting groups (-N3) into The T-cell membrane, to build human-derived T-cell artificial receptors, viruses wrapped in nanomaterials (PEI-DBCO), the dbCO group on the surface of the virus particles and T-cell artificial receptors (-N3) to produce an efficient, specific biopostocis reaction, to promote the interaction of the virus and T-cells, and thus enhance the interaction of T-cells.
this bioorthogonal-based artificial receptor/ligand strategy can be applied to a variety of T-cell engineering modifications, which can increase the transduction efficiency of ordinary lentivirus (Lentivirus/GFP) in human primary T cells to 70-80%.
at the same time, the virus transduction technology has good biosecurity and will not interfere with T-cell amplification and anti-tumor activity.
in cd19 CAR-T cell preparation, the artificial receptor-guided gene transduction technology increased the yield of CAR-T-positive cells by 4 times, exhibited an effective anti-tumor effect in in vitro and B lymphoma-transplanted NOD/SCID mouse models, and significantly reduced THE CAR-T cell dose, which will help to reduce the potential side effects of cytokine storm (CRS) and neurotoxicity in clinical treatment.
the artificial receptor-guided viral gene transduction strategy provides a new technology for the engineering of the original T-cell.
the project has been supported by the National Natural Science Foundation, the Ministry of Science and Technology international cooperation, the Guangdong Nanomedicine Key Laboratory, Shenzhen Science and Technology Program, etc.
related research: T-cell biofactory found that nibe-funded researchers have turned T-cells into drug factories to find cells in the body that carry specific diseases and then produce therapeutic proteins for diseased cells. Dr. Parijat Bhatnagar, a senior author of the
and director of cell medicine at the SRI International Center for Chemical Biology in Menlo Park, California, and his colleagues designed the t-cell "biofactory" to target cell diseases directly in the body while minimizing damage to surrounding healthy cells, the study was published in Advanced Biological Systems.
Dr. David Rampulla, director of the Synthetic Biology Technology Development Program at the National Institute of Biomedical Imaging and Bioengineering, said the researchers have used T cells to move around the body, destroying cells that appear to be abnormal, and adding some additional therapeutic significance and reactive functions.
this new cell-based tool to direct t-cells to target specific diseases, this work is a great example of synthetic biology, which involves redesigning existing natural biological systems for specific purposes.
T cells naturally enter the tissue from the blood, a process known as spillage, which patrols abnormal cells.
designed a new signaling pathway in T cells, utilizing this innate external seepage.
it transforms T-cells into a cell-based drug delivery system, which we call T-cell biofactories.
this can be designed to look for specific diseases in individuals, such as viral infections or certain types of cancer, and then synthesize a therapeutic protein to neutralise the disease.
, for example, to kill cells carrying influenza viruses, the researchers inserted a DNA sequence on the surface of the t-cell biological plant that encodes the flu-identifying protein.
this module is called sensors, and another important DNA sequence is the coding sequence of therapeutic proteins specifically designed to neutralize influenza viruses.
this module is called an effector.
the effector is activated when the sensor identifies the host cell infected with influenza.
these DNA sequences are modular and can be exchanged to redirect t-cell biofactories to different disease targets.
the activity and specificity of t-cell biofactories were confirmed for the first time in mice carrying human ovarian tumors.
in the test, the sensor module is a protein that binds to ovarian cancer cells.
, unlike the effect protein that kills tumors, the researchers implanted a gene that produces bioluminescence proteins.
this bioluminescence allows the team to observe whether the binding of the t-cell biofactory to ovarian cancer cells causes the effect protein to be released within the tumor, and the control biofactory does not contain sensor modules.
the sensor molecules on the surface of the t-cell biofactory interact with diseased cells, not healthy cells.
then plant to produce therapeutic-effect proteins that attack and destroy diseased cells.
Photo: Parijat Bhatnagar, SRI International, Menlo Park, CA. 24 hours after injection, the amount of reported protein released by the t-cell biofactory was significantly higher than in the control group.
fluorescence peaks in 48 hours and lasts for 72 hours.
first trial has demonstrated the feasibility of a t-cell-based system that can target specific cell-based diseases and express an effect protein at the disease site.
researchers are enthusiastic about the preliminary results and hope to have a system to avoid systemic infusions of drugs that tend to damage health and diseased tissue.
reprogramable system scants therapeutic proteins only when diseased cells are encountered in biological plants, limiting damage to normal tissue.
Research/From: National Institutes of Health Reference Journal Literature: Advanced Biosystems DOI: 10.1002/adbi.201800210 Source: Boko Park, Shenzhen Institute of Advanced Technology.