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Challenges and Opportunities in Downstream Separation Processes for Mesenchymal Stromal Cells Cultured in Microcarrier-based Stirred Suspension Bioreactors Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-08-12 Inaara Mawji, Erin L. Roberts, Tiffany Dang, Brett Abraham, Michael S. Kallos
Mesenchymal stromal cells (MSC) are a promising platform for regenerative medicine applications because of their multi-lineage differentiation abilities and ease of collection, isolation, and growth ex-vivo. To meet the demand for clinical applications, large scale manufacturing will be required using three-dimension culture platforms in vessels such as stirred suspension bioreactors. As MSCs are an
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Cover Image, Volume 119, Number 9, September 2022 Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-08-13 Izel Koyuturk, Surbhi Kedia, Anna Robotham, Alexandra Star, Denis Brochu, Janelle Sauvageau, John Kelly, Michel Gilbert, Yves Durocher
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Engineered Cas13 variants with minimal collateral RNA targeting Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-12
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A Kinetic Framework for Modeling Oleochemical Biosynthesis in E. coli Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-08-12 Jackson Peoples, Sophia Ruppe, Kathryn Mains, Elia C. Cipriano, Jerome M. Fox
Microorganisms build fatty acids with biocatalytic assembly lines, or fatty acid synthases (FASs), that can be repurposed to produce a broad set of fuels and chemicals. Despite their versatility, the product profiles of FAS-based pathways are challenging to adjust without experimental iteration, and off-target products are common. This study uses a detailed kinetic model of the E. coli FAS as a foundation
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Escherichia coli minicells with targeted enzymes as bioreactors for producing toxic compounds Metab. Eng. (IF 8.829) Pub Date : 2022-08-12 Seung-Jin Kim, Woojin Chang, Min-Kyu Oh
Formed by aberrant cell division, minicells possess functional metabolism despite their inability to grow and divide. Minicells exhibit not only superior stability when compared with bacterial cells but also exceptional tolerance—characteristics that are essential for a de novo bioreactor platform. Accordingly, we engineered minicells to accumulate protein, ensuring sufficient production capability
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Abalos Therapeutics---arenaviruses take on cancer Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-12
After >20 years of research at the intersection of virology and immunology, two brothers have launched a venture seeking to turn arenaviruses into an anticancer virotherapy.
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Accessible bioengineered corneal tissue to address a blinding disease globally Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-11
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High-fidelity Cas13 variants for targeted RNA degradation with minimal collateral effects Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-11 Huawei Tong, Jia Huang, Qingquan Xiao, Bingbing He, Xue Dong, Yuanhua Liu, Xiali Yang, Dingyi Han, Zikang Wang, Xuchen Wang, Wenqin Ying, Runze Zhang, Yu Wei, Chunlong Xu, Yingsi Zhou, Yanfei Li, Minqing Cai, Qifang Wang, Mingxing Xue, Guoling Li, Kailun Fang, Hainan Zhang, Hui Yang
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Bioengineered corneal tissue for minimally invasive vision restoration in advanced keratoconus in two clinical cohorts Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-11 Mehrdad Rafat, Mahmoud Jabbarvand, Namrata Sharma, Maria Xeroudaki, Shideh Tabe, Raha Omrani, Muthukumar Thangavelu, Anthony Mukwaya, Per Fagerholm, Anton Lennikov, Farshad Askarizadeh, Neil Lagali
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Ligand conjugated lipid-based nanocarriers for cancer theranostics Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-08-11 Rahul Kumar, Daphika S Dkhar, Rohini Kumari, Divya Supratim Mahapatra, Ananya Srivastava, Vikash Kumar Dubey, Pranjal Chandra
Cancer is one of the major health-related issues affecting the population worldwide and subsequently accounts for the second-largest death. Genetic and epigenetic modifications in oncogenes or tumor suppressor genes affect the regulatory systems that lead to the initiation and progression of cancer. Conventional methods, including chemotherapy/radiotherapy/appropriate combinational therapy and surgery
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Microfluidic single-cell scale-down bioreactors: A proof-of-concept for the growth of Corynebacterium glutamicum at oscillating pH values Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-08-10 Sarah Täuber, Luisa Blöbaum, Valentin Steier, Marco Oldiges, Alexander Grünberger
In large-scale bioreactors, gradients in cultivation parameter such as oxygen, substrate and pH result in fluctuating cell environments. pH fluctuations were identified as a critical parameter for bioprocess performance. Traditionally, scale-down systems at the laboratory scale are used to analyze the effects of fluctuating pH values on strain and thus process performance. Here, we demonstrate the
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Kluyveromyces marxianus as a microbial cell factory for lignocellulosic biomass valorisation Biotechnol. Adv. (IF 17.681) Pub Date : 2022-08-08 Marlene Baptista, Lucília Domingues
The non-conventional yeast Kluyveromyces marxianus is widely used for several biotechnological applications, mainly due to its thermotolerance, high growth rate, and ability to metabolise a wide range of sugars. These cell traits are strategic for lignocellulosic biomass valorisation and strain diversity prompts the development of robust chassis, either with improved tolerance to lignocellulosic inhibitors
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Self-supervised learning in medicine and healthcare Nat. Biomed. Eng. (IF 29.234) Pub Date : 2022-08-11 Rayan Krishnan, Pranav Rajpurkar, Eric J. Topol
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Rapid detection of SARS-CoV-2 RNA in saliva via Cas13 Nat. Biomed. Eng. (IF 29.234) Pub Date : 2022-08-11 Sita S. Chandrasekaran, Shreeya Agrawal, Alison Fanton, Aditya R. Jangid, Bérénice Charrez, Arturo M. Escajeda, Sungmin Son, Roger Mcintosh, Huyen Tran, Abdul Bhuiya, María Díaz de León Derby, Neil A. Switz, Maxim Armstrong, Andrew R. Harris, Noam Prywes, Maria Lukarska, Scott B. Biering, Dylan C. J. Smock, Amanda Mok, Gavin J. Knott, Qi Dang, Erik Van Dis, Eli Dugan, Shin Kim, Tina Y. Liu, Erica A
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Development of a nonauxotrophic L-homoserine hyperproducer in Escherichia coli by systems metabolic engineering Metab. Eng. (IF 8.829) Pub Date : 2022-08-10 Mengmeng Cai, Zhenqiang Zhao, Xiangfei Li, Yuanyi Xu, Meijuan Xu, Zhiming Rao
L-Homoserine is a valuable amino acid as a platform chemical in the synthesis of various important compounds. Development of microbial strains for high-level L-homoserine production is an attractive research direction in recent years. Herein, we converted a wild-type Escherichia coli to a non-auxotrophic and plasmid-free hyperproducer of L-homoserine using systematically metabolic engineer strategies
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A novel WRKY34-bZIP3 module regulates phenolic acid and tanshinone biosynthesis in Salvia miltiorrhiza Metab. Eng. (IF 8.829) Pub Date : 2022-08-05 Min Shi, Ruiyan Zhu, Yi Zhang, Siwei Zhang, Tingyao Liu, Kunlun Li, Shucan Liu, Leran Wang, Yao Wang, Wei Zhou, Qiang Hua, Guoyin Kai
Phenolic acids and tanshinones are main bioactive compounds produced in Salvia miltiorrhiza widely used in treatment of cardiovascular diseases, which could be promoted by abscisic acid elicitation. However, the regulation mechanism remained to be elucidated. An ABA-inducible IIa WRKY transcription factor (TF) named SmWRKY34 exhibiting high homology with AtWRKY40 was isolated. SmWRKY34 exhibited a
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Epigenomics Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-09
Recent patents relating to epigenomic analyses, modification and engineering.
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Second-quarter biotech job picture Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-09 Michael Francisco
A quarterly snapshot of job expansions, reductions and availability in the biotech and pharma sectors.
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Patents benefit patients and patent reform would spur diagnostic and therapeutic development Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-09 Laura A. Coruzzi
Patients need the patent system to spur the investment necessary for the continued development of life-saving diagnostics and therapies.
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Can hackathons unlock a new talent pool from the developing world? Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-09 Timothy P. Jenkins, Nicolas Lopez Carranza, Amy Bray, Karim Beguir, Andreas H. Laustsen
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People Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-09
Recent moves of note in and around the biotech and pharma industries.
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HER3-addicted tumors: how biotechs are closing in Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-09
The elusive HER3, known to drive aggressive cancers, may finally be toppled by once-abandoned antibody drugs.
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mRNA printers kick-start personalized medicines for all Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-09
mRNA printers will bring low-cost vaccines and made-to-order treatments for a range of different diseases.
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Role, Relevance, and Possibilities of In vitro fermentation models in human dietary, and gut-microbial studies Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-08-08 Vineet Singh, HyunWoo Son, GyuDae Lee, Sunwoo Lee, Tatsuya Unno, Jae-Ho Shin
Dietary studies play a crucial role in determining the health-benefiting effects of most food substances, including prebiotics, probiotics, functional foods, and bioactive compounds. Such studies involve gastrointestinal digestion and colonic fermentation of dietary substances. In colonic fermentation, any digested food is further metabolized in the gut by the residing colonic microbiota, causing a
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Generation of T-cell-receptor-negative CD8αβ-positive CAR T cells from T-cell-derived induced pluripotent stem cells Nat. Biomed. Eng. (IF 29.234) Pub Date : 2022-08-08 Sjoukje J. C. van der Stegen, Pieter L. Lindenbergh, Roseanna M. Petrovic, Hongyao Xie, Mame P. Diop, Vera Alexeeva, Yuzhe Shi, Jorge Mansilla-Soto, Mohamad Hamieh, Justin Eyquem, Annalisa Cabriolu, Xiuyan Wang, Ramzey Abujarour, Tom Lee, Raedun Clarke, Bahram Valamehr, Maria Themeli, Isabelle Riviere, Michel Sadelain
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A DNA Typewriter in living cells. Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-01 Eleni Kotsiliti
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Drug pipeline 2Q22 - a downturn in approvals. Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-01 Laura DeFrancesco
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A lab-on-a-chip for the concurrent electrochemical detection of SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies in saliva and plasma Nat. Biomed. Eng. (IF 29.234) Pub Date : 2022-08-08 Devora Najjar, Joshua Rainbow, Sanjay Sharma Timilsina, Pawan Jolly, Helena de Puig, Mohamed Yafia, Nolan Durr, Hani Sallum, Galit Alter, Jonathan Z. Li, Xu G. Yu, David R. Walt, Joseph A. Paradiso, Pedro Estrela, James J. Collins, Donald E. Ingber
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Orna Therapeutics: circular logic Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-05
In the ascendant world of mRNA medicines, circular RNA shows promise as an alternative way for making proteins inside human cells.
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Design of a genetically encoded biosensor to establish a high-throughput screening platform for L-cysteine overproduction Metab. Eng. (IF 8.829) Pub Date : 2022-07-31 Jinshan Gao, Muhua Du, Jinhua Zhao, Yue zhang, Ning Xu, Huanmin Du, Jiansong Ju, Liang Wei, Jun Liu
Metabolic engineering seeks to rewire the metabolic network of cells for the efficient production of value-added compounds from renewable substrates. However, it remains challenging to evaluate and identify strains with the desired phenotype from the vast rational or random mutagenesis library. One effective approach to resolve this bottleneck is to design an efficient high-throughput screening (HTS)
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De novo production of versatile oxidized kaurene diterpenes in Escherichia coli Metab. Eng. (IF 8.829) Pub Date : 2022-08-05 Yuwei Sun, Zhuo Chen, Guangyi Wang, Huajun Lv, Yaping Mao, Ke Ma, Yong Wang
The oxidized kaurene (Ox-Kau) compounds are the core structures of many important diterpenoids with biological activities and economical values. However, easy access to diverse Ox-Kau products is still limited by low natural abundance, and large-scale manufacture remain challenging due to lack of proper heterologous production. To achieve an abundant source alternative to natural extracts, we here
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Designer phospholipids – structural retrieval, chemo-/bio- synthesis and isotopic labeling Biotechnol. Adv. (IF 17.681) Pub Date : 2022-07-30 Oliver Bogojevic, Jens Vinge Nygaard, Lars Wiking, Calle Arrevång, Zheng Guo
Phospholipids are unique and versatile molecules, essential in a variety of biological systems. Moreover, their diverse structures and amphiphilic properties endorse their indispensable and unparalleled roles in research and industrial-related applications. However, in most cases of applications, naturally occurring phospholipids are either deficit in structural variety or insufficient in quantity;
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The digital phenotype of vaccination Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-03 Giorgio Quer, Eric J. Topol, Steven R. Steinhubl
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Increase vigilance against cyberattacks Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-03
The biotech sector must devote more resources to cybersecurity — especially those companies that are manufacturers of essential medical products.
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The BioInnovation Institute as a catalyst for European life science startup creation Nat. Biotechnol. (IF 68.164) Pub Date : 2022-08-03 Jens Nielsen, Markus J. Herrgård, Bobby Soni
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Delineating biosynthesis of Huperzine A, A plant-derived medicine for the treatment of Alzheimer's disease Biotechnol. Adv. (IF 17.681) Pub Date : 2022-07-30 Xiao Li, Wei Li, Pingfang Tian, Tianwei Tan
Huperzine A (HupA) is a plant-derived lycopodium alkaloid used for the treatment of Alzheimer's disease due to its inhibition against acetylcholinesterase. Currently, industrial production of HupA relies primarily on direct extraction from Huperzia serrate, a perennial herbaceous plant. However, this strategy cannot satisfy the increasing demand for HupA due to scarcity of H. serrate whose growth is
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Multimodular vascularized bone construct comprised of vasculogenic and osteogenic microtissues Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-08-03 Nicholas G. Schott, Huy Vu, Jan P. Stegemann
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Fabrication and in vitro evaluation of 3D printed porous silicate substituted calcium phosphate scaffolds for bone tissue engineering Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-08-03 Dechun Chen, Guanghua Chen, Xin Zhang, Jingtao Chen, Jinmeng Li, Kunlong Kang, Weitao He, Yuanhang Kong, Leilei Wu, Bo Su, Kui Zhao, Daiwei Si, Xintao Wang
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Spheroid culture for chondrocytes triggers the initial stage of endochondral ossification Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-08-03 Jeonghyun Kim, Kosei Tomida, Takeo Matsumoto, Taiji Adachi
Endochondral ossification is the process of bone formation derived from growing cartilage duringskeletal development. In previous studies, we provoked the osteocyte differentiation of osteoblast precursor cells under a three-dimensional (3D) culture model. To recapitulate the endochondral ossification, the present study utilized the self-organized scaffold-free spheroid model reconstructed by pre-chondrocyte
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13C metabolic flux analysis clarifies distinct metabolic phenotypes of cancer cell spheroid mimicking tumor hypoxia Metab. Eng. (IF 8.829) Pub Date : 2022-07-31 Shingo Noguchi, Kenichi Wakita, Fumio Matsuda, Hiroshi Shimizu
Cancer cells adapt their intracellular energy metabolism to the oxygen-deprived tumor microenvironment (TME) to ensure tumor progression. This adaptive mechanism has focused attention on the metabolic phenotypes of tumor cells under hypoxic TME for developing novel cancer therapies. Although widely used monolayer (2D) culture does not fully reflect in vivo hypoxic TME, spheroid (3D) culture can produce
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Systems metabolic engineering of Corynebacterium glutamicum eliminates all by-products for selective and high-yield production of the platform chemical 5-aminovalerate Metab. Eng. (IF 8.829) Pub Date : 2022-07-30 Christina Rohles, Sarah Pauli, Gideon Gießelmann, Michael Kohlstedt, Judith Becker, Christoph Wittmann
5-aminovalerate (AVA) is a platform chemical of substantial commercial value to derive nylon-5 and five-carbon derivatives like δ-valerolactam, 1,5-pentanediol, glutarate, and 5-hydroxyvalerate. De novo bio-production synthesis of AVA using metabolically engineered cell factories is regarded as exemplary route to provide this chemical in a sustainable way. So far, this route is limited by low titers
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Development of versatile affinity-based system for one step purification process: Case of Group A Streptococcus vaccine Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-07-30 Anne Chevrel, Leo Candela, Elisa Innocenti, Carolin Golibrzuch, Romas Skudas, Achim Schwämmle, Manuel J. T. Carrondo, Olivier Kitten, Mikkel Nissum, Ricardo J. S. Silva
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BEHAV3D: an imaging and transcriptomics platform that unravels T cell antitumor activity Nat. Biotechnol. (IF 68.164) Pub Date : 2022-07-28
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Efficient in vivo base editing via single adeno-associated viruses with size-optimized genomes encoding compact adenine base editors Nat. Biomed. Eng. (IF 29.234) Pub Date : 2022-07-28 Jessie R. Davis, Xiao Wang, Isaac P. Witte, Tony P. Huang, Jonathan M. Levy, Aditya Raguram, Samagya Banskota, Nabil G. Seidah, Kiran Musunuru, David R. Liu
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Pressure-dependent fouling behavior during sterile filtration of mRNA-containing lipid nanoparticles Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-07-29 Kevork Oliver Messerian, Anton Zverev, Jack F. Kramarczyk, Andrew L. Zydney
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Strategies for overcoming the limitations of enzymatic carbon dioxide reduction Biotechnol. Adv. (IF 17.681) Pub Date : 2022-07-28 Qiyong Liao, Wenfang Liu, Zihui Meng
The overexploitation of fossil fuels has led to a significant increase in atmospheric carbon dioxide (CO2) concentrations, thereby causing problems, such as the greenhouse effect. Rapid global climate change has caused researchers to focus on utilizing CO2 in a green and efficient manner. One of the ways to achieve this is by converting CO2 into valuable chemicals via chemical, photochemical, electrochemical
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New horizons in developing cell lysis methods: A review Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-07-28 Mohsen Danaeifar
Cell lysis is an essential step in many studies related to biology and medicine. Based on the scale and medium that cell lysis is carried out, there are three main types of the cell lysis: (1) lysis of the cells in the surrounding environment, (2) lysis of the isolated or cultured cells, and (3) single cell lysis. Conventionally, several cell lysis methods have been developed, such as freeze-thawing
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Recent developments in cell shipping methods Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-07-27 Shabnam Heydarzadeh, Sima Kheradmand Kia, Seti Boroomand, Mehdi Hedayati
As opposed to remarkable advances in the cell therapy industry, research reveal inexplicable difficulties associated with preserving and post-thawing cell death. Post cryopreservation apoptosis is a common occurrence that has attracted the attention of scientists to use apoptosis inhibitors. Transporting cells without compromising their survival and function is crucial for any experimental cell-based
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Improved production of heme using metabolically engineered Escherichia coli Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-07-27 Kyeong Rok Choi, Hye Eun Yu, Hoseong Lee, Sang Yup Lee
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Anhydride chemistry-based hexanoylation of polyethylenimine increases transfection efficiency and expression of tagged DNA for therapeutic proteins in cultured cells Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-07-27 Goutam Ulgekar, Dilpreet Kaur, Venkateswaran Ganesan, Souvik Sen Sharma, Nirmalya Ganguli, Subeer S. Majumdar
Transfection of nucleic acid molecules into mammalian cells can be facilitated using viral vectors, electroporation, or biocompatible cationic materials. However, safety issues and the requirement of specialized equipment limits the use of viral vectors and physical methods of transfection like electroporation and microinjection, respectively. Biocompatible cationic lipids and polymers like branch
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Precision cancer targeting with antibody pairs Nat. Biotechnol. (IF 68.164) Pub Date : 2022-07-25 Robert T. Lawrence, Peter D. Senter
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Ras-mutant cancers are sensitive to small molecule inhibition of V-type ATPases in mice Nat. Biotechnol. (IF 68.164) Pub Date : 2022-07-25 Bhairavi Tolani, Anna Celli, Yanmin Yao, Yong Zi Tan, Richard Fetter, Christina R. Liem, Adam J. de Smith, Thamiya Vasanthakumar, Paola Bisignano, Adam D. Cotton, Ian B. Seiple, John L. Rubinstein, Marco Jost, Jonathan S. Weissman
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Logic-gated antibody pairs that selectively act on cells co-expressing two antigens Nat. Biotechnol. (IF 68.164) Pub Date : 2022-07-25 Simone C. Oostindie, Derek A. Rinaldi, Gijs G. Zom, Michael J. Wester, Desiree Paulet, Kusai Al-Tamimi, Els van der Meijden, Jennifer R. Scheick, Tessa Wilpshaar, Bart de Jong, Marloes Hoff-van den Broek, Rachel M. Grattan, Janita J. Oosterhoff, Julie Vignau, Sandra Verploegen, Peter Boross, Frank J. Beurskens, Diane S. Lidke, Janine Schuurman, Rob N. de Jong
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Uncovering the mode of action of engineered T cells in patient cancer organoids Nat. Biotechnol. (IF 68.164) Pub Date : 2022-07-25 Johanna F. Dekkers, Maria Alieva, Astrid Cleven, Farid Keramati, Amber K. L. Wezenaar, Esmée J. van Vliet, Jens Puschhof, Peter Brazda, Inez Johanna, Angelo D. Meringa, Heggert G. Rebel, Maj-Britt Buchholz, Mario Barrera Román, Amber L. Zeeman, Sam de Blank, Domenico Fasci, Maarten H. Geurts, Annelisa M. Cornel, Else Driehuis, Rosemary Millen, Trudy Straetemans, Mara J. T. Nicolasen, Tineke Aarts-Riemens
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Production of retinoic acid by engineered Saccharomyces cerevisiae using an endogenous aldehyde dehydrogenase Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-07-26 Qiongyue Hu, Hongwei Yu, Lidan Ye
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Production of zinc protoporphyrin IX by metabolically engineered Escherichia coli Biotechnol. Bioeng. (IF 4.395) Pub Date : 2022-07-26 Kyeong Rok Choi, Hye Eun Yu, Sang Yup Lee