In August 2022, Dr. Zheng attended the eighth Cold Spring Harbour meeting on Genome Engineering: CRISPR Frontiers. GUIDE-Seq Enables Genome-Wide Profiling of Off-Target Cleavage by CRISPR-Cas Nucleases. doi: 10.1007/s00262-018-2193-1, 146. CRISPR: A New Way for Scientists to Edit DNA - Frontiers for Young Minds Camacho-Pereira J, Tarrago MG, Chini CCS, Nin V, Escande C, Warner GM, et al. Brudno JN, Somerville RP, Shi V, Rose JJ, Halverson DC, Fowler DH, et al. Fri Jun 30 - Sat Jul 15 2023. Genome Engineering: CRISPR Frontiers 8/24 - 8/27. Generation of Knock-in Primary Human T Cells Using Cas9 Ribonucleoproteins. Am J Hematol (2019) 94:S504. doi: 10.1182/bloodadvances.2018017004, 48. Cheng M, Chen Y, Xiao W, Sun R, Tian Z. NK Cell-Based Immunotherapy for Malignant Diseases. doi: 10.1084/jem.20082013, 118. Front Immunol (2017) 8. doi: 10.3389/fimmu.2017.00360, 79. Although advancement in immunotherapy has been significant and durable, most cancer patients fail to respond to immunotherapy due to resistant tumor nature. Frontiers | Targeted modification of CmACO1 by CRISPR/Cas9 extends the Received: 12 December 2021; Accepted: 07 March 2022;Published: 05 April 2022. Over the last few years, scientists have adapted this bacterial defense system to be used in the laboratory to alter the DNA of various organisms. Zischewski J, Fischer R, Bortesi L. Detection of on-Target and Off-Target Mutations Generated by CRISPR/Cas9 and Other Sequence-Specific Nucleases. Join us at the CSHL Genome Engineering: CRISPR Frontiers meeting. Privacy doi: 10.1182/blood-2008-06-164103, 84. Bioinformatics (2014) 30:14735. Twitter CSHL Meetings NOTE: We cannot guarantee housing will be on campus. For these applications that lead to clinical cancer immunotherapy, the induced mutations by CRISPR-Cas9 should be highly precise and specific for the targeted loci with high on-target efficiency and low or no off-target activity. Cold Spring Harbor Meetings and Courses - Long Island, New York. Cold Spring Harbor Lab Genome Engineering: CRISPR Frontiers Graham C, Jozwik A, Pepper A, Benjamin R. Allogeneic CAR-T Cells: More Than Ease of Access? Nat Commun (2019) 10:4681. doi: 10.1038/s41467-019-12606-7, 11. In May 2023, Frontiers adopted a new reporting platform to be Counter 5 compliant, in line with industry standards. doi: 10.1038/cmi.2013.10, 5. Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia. Donate Now. doi: 10.1056/NEJMoa1708566, 35. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. Involvement of PD-L1 on Tumor Cells in the Escape From Host Immune System and Tumor Immunotherapy by PD-L1 Blockade. Singh N, Shi J, June CH, Ruella M. Genome-Editing Technologies in Adoptive T Cell Immunotherapy for Cancer. N Engl J Med (2018) 378:43948. However, due to some limitations, including transduction efficiency, off-target mutations, ethical questions, and the deficiency in scientific risk assessment, CRISPR/Cas9 gene-editing clinical trials have not been prevalent, especially for T and NK cells. Immunol Rev (2019) 290:8599. Somanchi SS, Senyukov VV, Denman CJ, Lee DA. TGF- receptor II (TGFBR2) KO with CRISPR/Cas9 was also shown to reduce CAR-T exhaustion and increase the anti-tumor activity of CAR-T cells (72). Academic/Media Private Room/Shared Bath Package: $1,235 EST, Synthetic sgRNA for CRISPR-Cas9 experiments, Homology-directed repair with a DNA donor oligo, Homology-directed repair with a plasmid donor, Screening validation and follow-up using engineered cell lines, Reverse transfection for high-throughput CRISPR studies, Seed sibling controls for RNAi hit validation, Cold Spring Harbor Lab Genome Engineering: CRISPR Frontiers. Enhanced Homology-Directed Human Genome Engineering by Controlled Timing of CRISPR/Cas9 Delivery. Aksoy P, Escande C, White TA, Thompson M, Soares S, Benech JC, et al. In another study the efficiency and indel rates in the created CAR-T cells, using CRISPR-Cas9-mediated multiplex gene editing, was quantified by both surveyor assay and tracking of indels by decomposition (TIDE) analysis (58). 14. Blood (2020) 136:22. Maria Jasin, Memorial Sloan Kettering Cancer Center TGF-Beta Inhibition via CRISPR Promotes the Long-Term Efficacy of CAR T Cells Against Solid Tumors. The meeting will begin at 7:30 pm on Wednesday, August 24 and run through lunch on Saturday, August 27, 2022. CRISPR gene editing technology has shown to be a very versatile tool for improving anti-tumor activity of NK cells and T-cells. Turtle CJ, Hanafi L-A, Berger C, Hudecek M, Pender B, Robinson E, et al. NK cells are distinguished from the other immune cells by possessing CD3- and CD56+ phenotype. CHANGE-Seq Reveals Genetic and Epigenetic Effects on CRISPR-Cas9 Genome-Wide Activity. Single Cell Analysis. doi: 10.1016/j.cell.2015.06.059, 173. Biochem Biophys Res Commun (2006) 345:138692. NK cells highly express CD38 on their surface. NK cells develop in the bone marrow (BM) and secondary lymphoid tissues such as, tonsils, spleen and lymph nodes (LNs) and they represent 5-20% of circulating lymphocytes in humans (77, 78). J Leukoc Biol (2019) 105:1297303. Our R&D team will be there to discuss advancements in the space. Genome Engineering: CRISPR . 2012; Cong et al. Salminen A, Allahyari Z, Gholizadeh S, McCloskey MC, Ajalik R, Cottle RN, Gaborski T, and McGrath JL. Hematol Am Soc Hematol Educ Prog (2020) 2020:5708. CD38 as a Regulator of Cellular NAD: A Novel Potential Pharmacological Target for Metabolic Conditions. One Bungtown Road, Cold Spring Harbor, NY 11724. Ugeskr Laeger (1988) 150:1013. Inhibition of Stromal Cell-Derived Factor-1alpha/CXCR4 Signaling Restores the Blood-Retina Barrier in Pericyte-Deficient Mouse Retinas. Genetical Engineering for NK and T Cell Immunotherapy With CRISPR/Cas9 Technology: Implications and Challenges. Additional safety measures will be in line with current NY and federal guidelines. The CSHL Meetings Abstracts Collection is a catalog of the Meeting title, the Meeting Organizers, the Organizers . Another important target to improve the NK cells function is CISH encoded by CIS gene. Protocol for Isolation, Stimulation and Functional Profiling of Primary and iPSC-Derived Human NK Cells. Some of them like GUIDE-seq, SITE-Seq and CHANGE-seq are based on the PCR amplification of pre-selected potential sites, which predicted by CRISPR/Cas9 design tools, and sequencing the PCR amplicons utilizing Sanger or NGS technologies (158160, 163). Neelapu SS, Tummala S, Kebriaei P, Wierda W, Gutierrez C, Locke FL, et al. Robbins GM, Wang M, Pomeroy EJ, Moriarity BS. Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 Gene Editing Technique in Xenotransplantation. jialing@princeton.edu. One Bungtown Road, Cold Spring Harbor, NY 11724 Pesce S, Greppi M, Tabellini G, Rampinelli F, Parolini S, Olive D, et al. PloS One (2015) 10:e0134927. doi: 10.3791/2540, 90. 91. doi: 10.1016/j.biotechadv.2016.12.003, 164. Epigenomic studies to understand mechanisms by which off-target mutations can impact cell fitness. doi: 10.1016/j.bbmt.2016.04.009, 82. (73) showed that CRISPR/cas9 KO of granulocyte-macrophage colony-stimulating factor (GM-CSF) decreased the side effects like cytokine release syndrome and neuroinflammation of CAR-T cell therapies and also improved the CAR-T cell anti-tumor activity in-vivo (73). B-Cell Depletion and Remissions of Malignancy Along With Cytokine-Associated Toxicity in a Clinical Trial of Anti-CD19 Chimeric-Antigen-ReceptorTransduced T Cells. Two patients with advanced refractory myeloma and one with metastatic sarcoma were treated with these CRISPR-edited cells (68). Student No-Housing Package: $985 Cell Stem Cell (2014) 15:123. Nat Commun (2014) 5:5507. doi: 10.1038/ncomms6507, 168. Cytokine Growth Factor Rev (2013) 24:2418. Huang RS, Lai MC, Shih HA, Lin S. A Robust Platform for Expansion and Genome Editing of Primary Human Natural Killer Cells. Sci Trans Med (2015) 7:303ra139303ra139. It has been used to identify essential genes as immune checkpoint targets, generate CAR-T and CAR-NK cells, construct TCR, understand signaling pathways, and screen for new druggable targets in immunotherapy (1, 710). Curr Pharm Des (2009) 15:231935. Hermanson DL, Ni Z, Kaufman DS. The Leading Strand Mol Cancer (2020) 19:120. doi: 10.1186/s12943-020-01238-x, 88. Yamamoto K, Blum R, Kaufman DS. You are cordially invited to participate in the ninth meeting on Genome Engineering: CRISPR Frontiers at Cold Spring Harbor Laboratory. Genetic and Epigenetic Modification of Human Primary NK Cells for Enhanced Antitumor Activity. Blood (2020) 136:241627. Academic/Media Private Room/Private Bath Package: $1,705 The meeting will begin at 7:30 pm on Wednesday, August 16 and end with the banquet on Saturday, August 19, and departures on Sunday morning August 20. doi: 10.1038/s41573-019-0051-2, 45. Int J Mol Sci (2021) 22. doi: 10.3390/ijms22073489, 71. We have applied for funds from government and industry to partially support graduate students and postdocs. Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors. doi: 10.1007/s00262-018-2281-2, 68. CD19 CART Cells of Defined CD4+:CD8+ Composition in Adult B Cell ALL Patients. Sterner etal. CRISPR are classes of repeated DNA sequences that act in coordination with CRISPR-associated (Cas) genes to devote bacterial and archaeal immunity against foreign raider phages and plasmid DNA (11). CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction Through an SIRT3-Dependent Mechanism. Hum Gene Ther (1996) 7:210112. A Decade's Perspective on DNA Sequencing Technology. CRISPR/Cas9-Based Genome Editing in the Era of CAR T Cell Immunotherapy. Hanada T, Kinjyo I, Inagaki-Ohara K, Yoshimura A. If you are submitting an abstract for an oral or poster presentation, please plan to attend the meeting in-person. CRISPR/Cas9 strategy has also been used to target PD-1, CTLA-4, LAG-3, and TIM-3 inhibitory molecules to overcome tumor mediated immune suppression and enhance CAR-T cell function (22, 69, 70). Pomeroy EJ, Hunzeker JT, Kluesner MG, Lahr WS, Smeester BA, Crosby MR, et al. J Vis Exp (2011) e2540. Scoville SD, Freud AG, Caligiuri MA. doi: 10.1016/j.ymthe.2019.10.009, 103. Corporate Virtual Package: $480, Late Fee (Registrations submitted after 5:00 p.m. Blocking the Natural Killer Cell Inhibitory Receptor NKG2A Increases Activity of Human Natural Killer Cells and Clears Hepatitis B Virus Infection in Mice. Late Corporate Virtual Package: $475, Meetings Miura H, Quadros RM, Gurumurthy CB, Ohtsuka M. Easi-CRISPR for Creating Knock-in and Conditional Knockout Mouse Models Using Long ssDNA Donors. Blood (2020) 136:33. Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity. doi: 10.1073/pnas.192461099, 134. Verhoeyen E. Advances in Foamy Virus Vector Technology and Disease Correction Could Speed the Path to Clinical Application. December 2022 Our foray into microbiology goes live: M3-seq is released on BioRxiv. doi: 10.1038/s41577-020-0306-5, 132. Some bacteria have a defense system called CRISPR/Cas9 that protects them from infection with viruses. Archives They can be distinguished from other lymphocytes by possessing TCR on their cell surface. T Cells Expressing CD19 Chimeric Antigen Receptors for Acute Lymphoblastic Leukaemia in Children and Young Adults: A Phase 1 Dose-Escalation Trial. CD33 Targeting Primary CAR-NK Cells Generated By CRISPR Mediated Gene Insertion Show Enhanced Anti-AML Activity.