Gene therapy is known highly effective for treatment of many diseases;however,its wide use has been severely bottlenecked by lack of safe and effective delivery vectors[1].Cationic polymers are safe nonviral gene vect...Gene therapy is known highly effective for treatment of many diseases;however,its wide use has been severely bottlenecked by lack of safe and effective delivery vectors[1].Cationic polymers are safe nonviral gene vectors with great potential for large-scale applications[2],and widely used to condense the large macromolecules into cationic polymer/DNA complexes(polyplexes)nanoparticles,protect-展开更多
Engineered T cells expressing chimeric antigen receptor(CAR)exhibit high response rates in B-cell malignancy treatments and possess therapeutic potentials against various diseases.However,the complicated ex vivo produ...Engineered T cells expressing chimeric antigen receptor(CAR)exhibit high response rates in B-cell malignancy treatments and possess therapeutic potentials against various diseases.However,the complicated ex vivo production process of CAR-T cells limits their application.Herein,we use virus-mimetic fusogenic nanovesicles(FuNVs)to produce CAR-T cells in vivo via membrane fusion-mediated CAR protein delivery.Briefly,the FuNVs are modified using T-cell fusogen,adapted from measles virus or reovirus fusogens via displaying anti-CD3 single-chain variable fragment.The FuNVs can efficiently fuse with the T-cell membrane in vivo,thereby delivering the loaded anti-CD19(aCD19)CAR protein onto T-cells to produce aCD19 CAR-T cells.These aCD19 CAR-T cells alone or in combination with anti-OX40 antibodies can treat B-cell lymphoma without inducing cytokine release syndrome.Thus,our strategy provides a novel method for engineering T cells into CAR-T cells in vivo and can further be employed to deliver other therapeutic membrane proteins.展开更多
The integrity of the neuronal membrane is crucial for its function and cellular survival; thus, ineffective repair of damaged membranes may be one of the key elements underlying the neuronal degeneration and overall f...The integrity of the neuronal membrane is crucial for its function and cellular survival; thus, ineffective repair of damaged membranes may be one of the key elements underlying the neuronal degeneration and overall functional loss that occurs after spinal cord injury （SCI）. It has been shown that polyethylene glycol （PEG） can reseal axonal membranes following various injuries in multiple in vitro and in vivo injury models. In addition, PEG may also directly prevent the effects of mitochondria-derived oxidative stress on intracellular components. Thus, PEG repairs mechanically injured cells by at least two distinct pathways： resealing of the disrupted plasma membrane and direct protection of mitochondria. Besides repairing primary membrane damage, PEG treatment also results in significant attenuation of oxidative stress, likely due to its capacity to reseal the membrane, thereby breaking the cycle of cellular damage and free-radical production. Based on this, in addition to the practicality of its application, we expect that PEG may be established as an effective treatment for SCI where membrane disruption and mitochondriai damage are implicated.展开更多
文摘Gene therapy is known highly effective for treatment of many diseases;however,its wide use has been severely bottlenecked by lack of safe and effective delivery vectors[1].Cationic polymers are safe nonviral gene vectors with great potential for large-scale applications[2],and widely used to condense the large macromolecules into cationic polymer/DNA complexes(polyplexes)nanoparticles,protect-
基金This work was supported by the National Key R&D Program of China(2022YFB3808100)the National Natural Science Foundation of China(32271442,52130301,and 82072048)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2022B1515020025)the Science and Technology Program of Guangzhou,China(202103030004)the Fundamental Research Funds for the Central Universities(2022ZYGXZR102).
文摘Engineered T cells expressing chimeric antigen receptor(CAR)exhibit high response rates in B-cell malignancy treatments and possess therapeutic potentials against various diseases.However,the complicated ex vivo production process of CAR-T cells limits their application.Herein,we use virus-mimetic fusogenic nanovesicles(FuNVs)to produce CAR-T cells in vivo via membrane fusion-mediated CAR protein delivery.Briefly,the FuNVs are modified using T-cell fusogen,adapted from measles virus or reovirus fusogens via displaying anti-CD3 single-chain variable fragment.The FuNVs can efficiently fuse with the T-cell membrane in vivo,thereby delivering the loaded anti-CD19(aCD19)CAR protein onto T-cells to produce aCD19 CAR-T cells.These aCD19 CAR-T cells alone or in combination with anti-OX40 antibodies can treat B-cell lymphoma without inducing cytokine release syndrome.Thus,our strategy provides a novel method for engineering T cells into CAR-T cells in vivo and can further be employed to deliver other therapeutic membrane proteins.
文摘The integrity of the neuronal membrane is crucial for its function and cellular survival; thus, ineffective repair of damaged membranes may be one of the key elements underlying the neuronal degeneration and overall functional loss that occurs after spinal cord injury （SCI）. It has been shown that polyethylene glycol （PEG） can reseal axonal membranes following various injuries in multiple in vitro and in vivo injury models. In addition, PEG may also directly prevent the effects of mitochondria-derived oxidative stress on intracellular components. Thus, PEG repairs mechanically injured cells by at least two distinct pathways： resealing of the disrupted plasma membrane and direct protection of mitochondria. Besides repairing primary membrane damage, PEG treatment also results in significant attenuation of oxidative stress, likely due to its capacity to reseal the membrane, thereby breaking the cycle of cellular damage and free-radical production. Based on this, in addition to the practicality of its application, we expect that PEG may be established as an effective treatment for SCI where membrane disruption and mitochondriai damage are implicated.
