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Biomaterial-assisted biotherapy:A brief review of biomaterials used in drug delivery,Vaccine development,gene therapy,and stem cell therapy

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Bioactive Materials 2022年第11期7卷 29-48页

作者： Xuejiao Han Aqu Alu Hongmei Liu Yi Shi Xiawei Wei Lulu Cai Yuquan Wei Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of BiotherapyNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduChina Personalized Drug Therapy Key Laboratory of Sichuan Province Department of PharmacySichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu610072China Sichuan Provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu610072China

Biotherapy has recently become a hotspot research topic with encouraging prospects in various fields due to a wide range of treatments applications,as demonstrated in preclinical and clinical studies.However,the broad applications of biotherapy have been limited by critical challenges,including the lack of safe and efficient de-livery systems and serious side effects.Due to the unique potentials of biomaterials,such as good biocompati-bility and bioactive properties,biomaterial-assisted biotherapy has been demonstrated to be an attractive strategy.The biomaterial-based delivery systems possess sufficient packaging capacity and versatile functions,enabling a sustained and localized release of drugs at the target sites.Furthermore,the biomaterials can provide a niche with specific extracellular conditions for the proliferation,differentiation,attachment,and migration of stem cells,leading to tissue regeneration.In this review,the state-of-the-art studies on the applications of bio-materials in biotherapy,including drug delivery,Vaccine development,gene therapy,and stem cell therapy,have been summarized.The challenges and an outlook of biomaterial-assisted biotherapies have also been discussed.

关键词： Biomaterial Biotherapy Drug delivery system Vaccine development Gene therapy Stem cell therapy

Recent insights for the emerging COVID-19:Drug discovery,therapeutic options and Vaccine development

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Asian Journal of Pharmaceutical Sciences 2021年第1期16卷 4-23页

作者： Yuefei Zhu Jia Li Zhiqing Pang Department of Biomedical Engineering Columbia UniversityNew York 10027USA Key Laboratory of Smart Drug Delivery Ministry of EducationSchool of PharmacyFudan UniversityShanghai 201203China Department of Biomedical Sciences Faculty of MedicineHealth and Human SciencesMacquarie UniversitySydney NSW 2109Australia

SARS-CoV-2 has been marked as a highly pathogenic coronavirus of COVID-19 disease into the human population,causing over 5.5 million confirmed cases worldwide.As COVID-19 has posed a global threat with significant human casualties and severe economic losses,there is a pressing demand to further understand the current situation and develop rational strategies to contain the drastic spread of the virus.Although there are no specific antiviral therapies that have proven effective in randomized clinical trials,currently,the rapid detection technology along with several promising therapeutics for COVID-19 have mitigated its drastic transmission.Besides,global institutions and corporations have commenced to parse out effective vaccines for the prevention of COVID-19.Herein,the present review will give exhaustive details of extensive researches concerning the drug discovery and therapeutic options for COVID-19 as well as some insightful discussions of the status of COVID-19.

关键词： Coronavirus COVID-19 SARS-CoV-2 Precise prevention and control Drug discovery Vaccine development

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Emerging Frontiers in Vaccine development: A Review of Changing Paradigm

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Journal of Biosciences and Medicines 2022年第7期10卷 123-145页

作者： Ishan Ghosh Mohit D. Gandhi Huntington Beach High School Huntington Beach USA Quantitative Pharmacology and Pharmacometrics ICON Early Clinical Development Lenexa USA

The technology behind Vaccine development varies significantly from one vaccine to another depending on the time when the vaccine was first developed. Over the years, the vaccine innovation time has significantly shortened with the advancement of knowledge in the fields of molecular and cell biology, and discoveries in the field of biotechnology. The first vaccines created were tested in a kind of trial-and-error approach which sometimes had deadly side effects. These vaccines used either living, weakened, or completely dead pathogens. The use of whole pathogen vaccines was seen to be time consuming and unpredictable because even though it would cause an immune response, it could vary from person to person, and always had the risk of pathogens returning to virulence causing sometimes fatal outcomes. The next major technology used to create vaccines was subunit vaccines which utilize purified antigens inactivated through various methods. This technology is quite prevalent among the vaccines that are currently in circulation, making them quite effective, and free from fatal side effects. The viral vector vaccine technology has been around for a few decades and utilizes knowledge of molecular genetics to the greatest extent. It uses intermediate vectors to deliver genetic instructions to trigger an immune response within the subject body. The introduction of nucleic acid vaccines is the newest technology and has come to a great deal of attention during the SARS-CoV-2 immunization efforts. The technology primarily utilizes the delivery of genetic information using messenger ribonucleic acid (mRNA) to create characteristic pathogen-specific proteins that in turn generate an immune response in the recipients.

关键词： vaccine Technology DNA vaccine mRNA vaccine COVID-19 vaccine Vaccine development

A proof of concept for neutralizing antibody-guided vaccine design against SARS-CoV-2

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National Science Review 2021年第8期8卷 147-157页

作者： Li Zhang Lei Cao Xing-Su Gao Bin-Yang Zheng Yong-Qiang Deng Jing-Xin Li Rui Feng Qian Bian Xi-Ling Guo Nan Wang Hong-Ying Qiu Lei Wang Zhen Cui Qing Ye Geng Chen Kui-Kui Lu Yin Chen Yu-Tao Chen Hong-Xing Pan Jiaping Yu Wenrong Yao Bao-Li Zhu Jianping Chen Yong Liu Cheng-Feng Qin Xiangxi Wang Feng-Cai Zhu National Health Commission of the People’s Republic of China Key Laboratory of Enteric Pathogenic Microbiology (Jiangsu Provincial Center for Disease Control and Prevention) Center for Global Health School of Public HealthNanjing Medical University CAS Key Laboratory of Infection and Immunity National Laboratory of MacromoleculesInstitute of BiophysicsChinese Academy of Sciences Guangzhou Regenerative Medicine and Health Guangdong Laboratory Jiangsu Rec-biotechnology Co.Ltd State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology

Mutations and transient conformational movements of the receptor binding domain(RBD) that make neutralizing epitopes momentarily unavailable present immune escape routes for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). To mitigate viral escape, we developed a cocktail of neutralizing antibodies(NAbs) targeting epitopes located on different domains of spike(S) protein. Screening of a library of monoclonal antibodies generated from peripheral blood mononuclear cells of COVID-19 convalescent patients yielded potent NAbs, targeting the N-terminal domain(NTD) and RBD domain of S, effective at n M concentrations. Remarkably, a combination of RBD-targeting NAbs and NTD-binding NAbs, FC05, enhanced the neutralization potency in cell-based assays and an animal model. Results of competitive surface plasmon resonance assays and cryo-electron microscopy(cryo-EM) structures of antigen-binding fragments bound to S unveil determinants of immunogenicity. Combinations of immunogens, identified in the NTD and RBD of S, when immunized in rabbits and macaques, elicited potent protective immune responses against SARS-CoV-2. More importantly, two immunizations of this combination of NTD and RBD immunogens provided complete protection in macaques against a SARS-CoV-2 challenge, without observable antibody-dependent enhancement of infection. These results provide a proof of concept for neutralization-based immunogen design targeting SARS-CoV-2 NTD and RBD.

关键词： SARS-CoV-2 neutralizing antibodies Vaccine development structure-based immunogen design

Adenovirus-mediated gene delivery:Potential applications for gene and cell-based therapies in the new era of personalized medicine

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Genes & Diseases 2017年第2期4卷 43-63页

作者： Cody S.Lee Elliot S.Bishop Ruyi Zhang Xinyi Yu Evan M.Farina Shujuan Yan Chen Zhao Zongyue Zeng Yi Shu Xingye Wu Jiayan Lei Yasha Li Wenwen Zhang Chao Yang Ke Wu Ying Wu Sherwin Ho Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf Russell R.Reid Tong-Chuan He The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA Laboratory of Craniofacial Biology and development Section of Plastic and Reconstructive SurgeryDepartment of SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical UniversityChongqing 400016China Department of Laboratory Medicine and Clinical Diagnostics The Affiliated Yantai HospitalBinzhou Medical UniversityYantai 264100China Department of Immunology and Microbiology Beijing University of Chinese MedicineBeijing 100029China

With rapid advances in understanding molecular pathogenesis of human diseases in the era of genome sciences and systems biology,it is anticipated that increasing numbers of therapeutic genes or targets will become available for targeted therapies.Despite numerous setbacks,efficacious gene and/or cell-based therapies still hold the great promise to revolutionize the clinical management of human diseases.It is wildly recognized that poor gene delivery is the limiting factor for most in vivo gene therapies.There has been a long-lasting interest in using viral vectors,especially adenoviral vectors,to deliver therapeutic genes for the past two decades.Among all currently available viral vectors,adenovirus is the most efficient gene delivery system in a broad range of cell and tissue types.The applications of adenoviral vectors in gene delivery have greatly increased in number and efficiency since their initial development.In fact,among over 2000 gene therapy clinical trials approved worldwide since 1989,a significant portion of the trials have utilized adenoviral vectors.This review aims to provide a comprehensive overview on the characteristics of adenoviral vectors,including adenoviral biology,approaches to engineering adenoviral vectors,and their applications in clinical and preclinical studies with an emphasis in the areas of cancer treatment,vaccination and regenerative medicine.Current challenges and future directions regarding the use of adenoviral vectors are also discussed.It is expected that the continued improvements in adenoviral vectors should provide great opportunities for cell and gene therapies to live up to its enormous potential in personalized medicine.

关键词： Adenovirus Adenoviral vector Cell therapy Gene transfer Gene therapy Oncolytic virus Regenerative medicine Vaccine development

Novel polysaccharide-protein conjugates provide an immunogenic 13-valent pneumococcal conjugate vaccine for S.pneumoniae

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Synthetic and Systems Biotechnology 2017年第1期2卷 49-58页

作者： Allison E.B.Turner Jonas E.Gerson Helen Y.So Daniel J.Krasznai Adrienne J.St.Hilaire Donald F.Gerson vaccine Research and development PnuVax Incorporated Headquarters134 Albert St.KingstonOntarioK7L 3V2Canada vaccine Research and development PnuVax Incorporated Laboratories6000 Royalmount Ave.MontrealQuebecH4P 2T1Canada

Pneumonia remains the single leading cause of childhood death worldwide.Despite the commercial availability of multiple pneumococcal conjugate vaccines(PCVs),high dosage cost and supply shortages prevent PCV delivery to much of the developing world.The current work presents high-yield pneumococcal conjugates that are immunogenic in animals and suitable for use in human Vaccine development.The 13-valent pneumococcal conjugate vaccine(PCV-13)investigated in this research incorporated serotypes 1,3,4,5,6A,6B,7F,9V,14,18C,19A,19F,and 23F.Pneumococcal polysaccharides(PnPSs)and CRM197 carrier protein were produced and purified in-house,and used to prepare PnPS-CRM conjugates using unique,cyanide-free,in vacuo glycation conjugation methods.In vitro characterization confirmed the generation of higher molecular weight PnPS-CRM conjugates low in free protein.In vivo animal studies were performed to compare PnuVax's PCV-13 to the commercially available PCV-13,Prevnar®13(Pfizer,USA).A boost dose was provided to all groups post-dose 1 at t?14 days.Post-dose 2 results at t?28 days showed that all 13 serotypes in PnuVax's PCV-13 were boostable.Per serotype IgG GMCs demonstrated that PnuVax's PCV-13 is immunogenic for all 13 serotypes,with 10 of the 13 serotypes statistically the same or higher than Prevnar®13 post-dose 2.As a result,the novel polysaccharideprotein conjugates developed in this work are highly promising for use in human PCV development.The in vacuo conjugation technique applied in this work could also be readily adapted to develop many other conjugate vaccines.

关键词： Pneumonia Vaccine development PCV Pneumococcal conjugate vaccine Polysaccharide Carrier protein In vacuo glycation

Recent progress on chikungunya virus research

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Virologica Sinica 2017年第6期32卷 441-453页

作者： Wenxi An Ningning Ge Yilin Cao Jin Sun Xia Jin Viral Disease and vaccine Translational Research Unit CAS Key Laboratory of Molecular Virology andImmunology Institut Pasteur of Shanghai Chinese Academy of Sciences Department of Biochemistry and Molecular Biology Pennsylvania State University State College College of Pharmaceutical Sciences Jilin University

Chikungunya virus(CHIKV) is an arbovirus transmitted by Aedes mosquitos in tropical and subtropical regions across the world. After decades of sporadic outbreaks, it re-emerged in Africa,Asia, India Ocean and America suddenly, causing major regional epidemics recently and becoming a notable global health problem. Infection by CHIKV results in a spectrum of clinical diseases including an acute self-limiting febrile illness in most individuals, a chronic phase of recurrent join pain in a proportion of patients, and long-term arthralgia for months to years for the unfortunate few. No specific anti-viral drugs or licensed vaccines for CHIKV are available so far. A better understanding of virus-host interactions is essential for the development of therapeutics and vaccines. To this end, we reviewed the existing knowledge on CHIKV's epidemiology, clinical presentation, molecular virology, diagnostic approaches, host immune response, Vaccine development, and available animal models. Such a comprehensive overview, we believe, will shed lights on the promises and challenges in CHIKV Vaccine development.

关键词： chikungunya virus(CHIKV) epidemiology molecular virology host immune response Vaccine development

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Control of malaria and other vector-borne protozoan diseases in the tropics: enduring challenges despite considerable progress and achievements

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Infectious Diseases of Poverty 2014年第1期3卷 1-14页

作者： Denis Zofou Raymond B Nyasa Dickson S Nsagha Fidele Ntie-Kang Henry D Meriki Jules Clement N Assob Victor Kuete Biotechnology Unit Faculty of ScienceUniversity of BueaP.O.Box 63BueaSouth West RegionCameroon Department of Public Health and Hygiene Faculty of Health SciencesUniversity of BueaBueaCameroon CEPAMOQ Faculty of ScienceUniversity of DoualaP.O.Box 8580DoualaCameroon Chemical and Bioactivity Information Centre Department of ChemistryUniversity of BueaP.O.Box 63BueaCameroon Department of Biomedical Sciences Faculty of Health SciencesUniversity of BueaBueaCameroon Department of Biochemistry University of DschangP.O.Box 67DschangCameroon

Vector-borne protozoan diseases represent a serious public health challenge,especially in the tropics where poverty together with vector-favorable climates are the aggravating factors.Each of the various strategies currently employed to face these scourges is seriously inadequate.Despite enormous efforts,vaccines-which represent the ideal weapon against these parasitic diseases—are yet to be sufficiently developed and implemented.Chemotherapy and vector control are therefore the sole effective attempts to minimize the disease burden.Nowadays,both strategies are also highly challenged by the phenomenon of drug and insecticide resistance,which affects virtually all interventions currently used.The recently growing support from international organizations and governments of some endemic countries is warmly welcome,and should be optimally exploited in the various approaches to drug and insecticide research and development to overcome the burden of these prevalent diseases,especially malaria,leishmaniasis,Human African Trypanosomiasis(HAT),and Chagas disease.

关键词： Malaria Vector-borne protozoan diseases African trypanosomiasis Chagas disease Leishmaniasis Vector control Chemotherapy Vaccine development

Evolutionary implications of Avian Infectious Bronchitis Virus(AIBV)analysis

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Cell Research 2006年第3期16卷 323-327页

作者： Peng Shi~(1,2) Li Yu~2 Yun-xin Fu~3 Jing-Fei Huang~1 Ke-Qin Zhang~2 Ya-ping Zhang~(1,2)1 Laboratory of Cellular and Molecular Evolution,and Molecular Biology of Domestic Animals,Kunming lnstitute of Zoology,Chinese Academy of Sciences,Kunming 650223,China 2 Laboratory for Conservation and Utilization of Bio-resource,Yunnan University,Kunming 650091,China 3 Human Genetics Center,University of Texas at Houston,Houston,Texas 77030,USA Laboratory of Cellular and Molecular Evolution and Molecular Biology of Domestic Animals Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650223 China.

For developing efficient vaccines,it is essential to identify which amino acid changes are most important to the sur-vival of the virus.We investigate the amino acid substitution features in the Avian Infectious Bronchitis Virus (AIBV)antigenic domain of a vaccine serotype (DE072) and a virulent viral strain (GA98) to better understand adaptive evo-lution of AIBV.In addition,the SARS Coronavirus (SARS-CoV) was also analyzed in the same way.It is interestingto find that extreme comparability exists between AIBV and SARS in amino acid substitution pattern.It suggests thatamino acid changes that result in overall shift of residue charge and polarity should be paid special attention to duringthe development of vaccines.

关键词： Avian Infectious Bronchitis Virus SARS Coronavirus positive selection adaptive evolution Vaccine development