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  1. Article ; Online: RGEN Editing of RNA and DNA: The Long and Winding Road from Catalytic RNAs to CRISPR to the Clinic.

    Sullenger, Bruce A

    Cell

    2020  Volume 181, Issue 5, Page(s) 955–960

    Abstract: The first clinical studies utilizing RNA-guided endonucleases (RGENs) to therapeutically edit RNA and DNA in cancer patients were recently published. These groundbreaking technological advances promise to revolutionize genetic therapy and, as I discuss, ... ...

    Abstract The first clinical studies utilizing RNA-guided endonucleases (RGENs) to therapeutically edit RNA and DNA in cancer patients were recently published. These groundbreaking technological advances promise to revolutionize genetic therapy and, as I discuss, represent the culmination of decades of innovative work to engineer RGENs for such editing applications.
    MeSH term(s) CRISPR-Cas Systems ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; DNA/genetics ; Endonucleases/metabolism ; Gene Editing/methods ; Gene Editing/trends ; Mutation ; RNA/genetics ; RNA Editing/genetics ; RNA Editing/physiology ; RNA, Catalytic/genetics ; RNA, Guide, CRISPR-Cas Systems/genetics
    Chemical Substances RNA, Catalytic ; RNA, Guide, CRISPR-Cas Systems ; RNA (63231-63-0) ; DNA (9007-49-2) ; Endonucleases (EC 3.1.-)
    Language English
    Publishing date 2020-06-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2020.04.050
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1167: Show issues Location:
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    Zs.MG 58: Show issues

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  2. Article ; Online: Reversible Aptamer Staining, Sorting, and Cleaning of Cells (Clean FACS) with Antidote Oligonucleotide or Nuclease Yields Fully Responsive Cells.

    Requena, Martin D / Yan, Amy / Llanga, Telmo / Sullenger, Bruce A

    Nucleic acid therapeutics

    2024  Volume 34, Issue 1, Page(s) 12–17

    Abstract: The ability to reverse the binding of aptamers to their target proteins has received considerable attention for developing controllable therapeutic agents. Recently, use of aptamers as reversible cell-sorting ligands has also sparked interest. Antibodies ...

    Abstract The ability to reverse the binding of aptamers to their target proteins has received considerable attention for developing controllable therapeutic agents. Recently, use of aptamers as reversible cell-sorting ligands has also sparked interest. Antibodies are currently utilized for isolating cells expressing a particular cell surface receptor. The inability to remove antibodies from isolated cells following sorting greatly limits their utility for many applications. Previously, we described how a particular aptamer-antidote oligonucleotide pair can isolate cells and clean them. Here, we demonstrate that this approach is generalizable; aptamers can simultaneously recognize more than one cell type during fluorescent activated cell sorting (FACS). Moreover, we describe a novel approach to reverse aptamer binding following cell sorting using a nuclease. This alternative strategy represents a cleaning approach that does not require the generation of antidote oligonucleotides for each aptamer and will greatly reduce the cost and expand the utility of Clean FACS.
    MeSH term(s) Antidotes ; Aptamers, Nucleotide/genetics ; Aptamers, Nucleotide/pharmacology ; Ligands ; Staining and Labeling ; Antibodies ; SELEX Aptamer Technique
    Chemical Substances Antidotes ; Aptamers, Nucleotide ; Ligands ; Antibodies
    Language English
    Publishing date 2024-01-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2639888-6
    ISSN 2159-3345 ; 2159-3337
    ISSN (online) 2159-3345
    ISSN 2159-3337
    DOI 10.1089/nat.2023.0050
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Protocol for purification of cells in their native state using reversible aptamer-antidote pairs.

    Requena, Martin D / Gray, Bethany Powell / Sullenger, Bruce A

    STAR protocols

    2023  Volume 4, Issue 3, Page(s) 102348

    Abstract: Cell isolation from complex mixtures is a key step in many clinical and research applications, but standard isolation methods may affect the cell's biology and are difficult to reverse. Here, we present a method to isolate and restore cells to their ... ...

    Abstract Cell isolation from complex mixtures is a key step in many clinical and research applications, but standard isolation methods may affect the cell's biology and are difficult to reverse. Here, we present a method to isolate and restore cells to their native state using an aptamer that binds epidermal growth factor receptor (EGFR+)cells and a complementary antisense oligonucleotide to reverse binding. For complete details on the use and execution of this protocol, please refer to Gray et al.
    MeSH term(s) Antidotes ; Oligonucleotides ; Oligonucleotides, Antisense ; Cell Separation
    Chemical Substances Antidotes ; Oligonucleotides ; Oligonucleotides, Antisense
    Language English
    Publishing date 2023-06-13
    Publishing country United States
    Document type Journal Article
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2023.102348
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Applications and future of aptamers that achieve rapid-onset anticoagulation.

    Yu, Haixiang / Frederiksen, James / Sullenger, Bruce A

    RNA (New York, N.Y.)

    2023  Volume 29, Issue 4, Page(s) 455–462

    Abstract: In this short Perspective, we discuss the history of, and recent progress toward, the development of aptamers that can serve as rapid onset anticoagulants during cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), and catheter-based ...

    Abstract In this short Perspective, we discuss the history of, and recent progress toward, the development of aptamers that can serve as rapid onset anticoagulants during cardiopulmonary bypass (CPB), extracorporeal membrane oxygenation (ECMO), and catheter-based diagnostic and interventional procedures, several million of which are performed each year worldwide. Aptamer anticoagulants provide potent and antidote-controllable anticoagulation and have low immunogenicity. New methods of aptamer isolation and engineering have not only improved the quality of aptamers, but also accelerated their development. Unfortunately, no aptamer identified to date can produce an anticoagulant effect as potent as that produced by unfractionated heparin (UFH), the standard anticoagulant for CPB. We have suggested several possible strategies to amplify the anticoagulant potency of existing aptamer anticoagulants.
    MeSH term(s) Heparin/pharmacology ; Aptamers, Nucleotide/pharmacology ; Aptamers, Nucleotide/therapeutic use ; Blood Coagulation ; Anticoagulants/pharmacology ; Anticoagulants/therapeutic use ; Antidotes/pharmacology
    Chemical Substances Heparin (9005-49-6) ; Aptamers, Nucleotide ; Anticoagulants ; Antidotes
    Language English
    Publishing date 2023-01-25
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1241540-6
    ISSN 1469-9001 ; 1355-8382
    ISSN (online) 1469-9001
    ISSN 1355-8382
    DOI 10.1261/rna.079503.122
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4777: Show issues Location:
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  5. Article: RGEN Editing of RNA and DNA: The Long and Winding Road from Catalytic RNAs to CRISPR to the Clinic

    Sullenger, Bruce A

    Cell. 2020 May 28, v. 181, no. 5

    2020  

    Abstract: The first clinical studies utilizing RNA-guided endonucleases (RGENs) to therapeutically edit RNA and DNA in cancer patients were recently published. These groundbreaking technological advances promise to revolutionize genetic therapy and, as I discuss, ... ...

    Abstract The first clinical studies utilizing RNA-guided endonucleases (RGENs) to therapeutically edit RNA and DNA in cancer patients were recently published. These groundbreaking technological advances promise to revolutionize genetic therapy and, as I discuss, represent the culmination of decades of innovative work to engineer RGENs for such editing applications.
    Keywords DNA ; catalytic activity ; clinical trials ; gene editing ; neoplasms ; patients ; ribozymes ; therapeutics
    Language English
    Dates of publication 2020-0528
    Size p. 955-960.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2020.04.050
    Database NAL-Catalogue (AGRICOLA)

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    In stock of ZB MED Bonn / Germany

    Z 75/702: Show issues
    Z 93: Show issues

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  6. Article ; Online: Aptamers Coming of Age at Twenty-Five.

    Sullenger, Bruce A

    Nucleic acid therapeutics

    2016  Volume 26, Issue 3, Page(s) 119

    Language English
    Publishing date 2016
    Publishing country United States
    Document type Editorial
    ZDB-ID 2639888-6
    ISSN 2159-3345 ; 2159-3337
    ISSN (online) 2159-3345
    ISSN 2159-3337
    DOI 10.1089/nat.2016.29001.sul
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  7. Article: Aptamer-programmable adeno-associated viral vectors as a novel platform for cell-specific gene transfer.

    Puzzo, Francesco / Zhang, Chuanling / Powell Gray, Bethany / Zhang, Feijie / Sullenger, Bruce A / Kay, Mark A

    Molecular therapy. Nucleic acids

    2023  Volume 31, Page(s) 383–397

    Abstract: Adeno-associated viruses (AAVs) are commonly used ... ...

    Abstract Adeno-associated viruses (AAVs) are commonly used for
    Language English
    Publishing date 2023-01-21
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2662631-7
    ISSN 2162-2531
    ISSN 2162-2531
    DOI 10.1016/j.omtn.2023.01.007
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  8. Article: An Aptamer That Rapidly Internalizes into Cancer Cells Utilizes the Transferrin Receptor Pathway.

    Song, Xirui / Yu, Haixiang / Sullenger, Cynthia / Gray, Bethany Powell / Yan, Amy / Kelly, Linsley / Sullenger, Bruce

    Cancers

    2023  Volume 15, Issue 8

    Abstract: Strategies to direct drugs specifically to cancer cells have been increasingly explored, and significant progress has been made toward such targeted therapy. For example, drugs have been conjugated into tumor-targeting antibodies to enable delivery ... ...

    Abstract Strategies to direct drugs specifically to cancer cells have been increasingly explored, and significant progress has been made toward such targeted therapy. For example, drugs have been conjugated into tumor-targeting antibodies to enable delivery directly to tumor cells. Aptamers are an attractive class of molecules for this type of drug targeting as they are high-affinity/high-specificity ligands, relatively small in size, GMP manufacturable at a large-scale, amenable to chemical conjugation, and not immunogenic. Previous work from our group revealed that an aptamer selected to internalize into human prostate cancer cells, called E3, can also target a broad range of human cancers but not normal control cells. Moreover, this E3 aptamer can deliver highly cytotoxic drugs to cancer cells as Aptamer-highly Toxic Drug Conjugates (ApTDCs) and inhibit tumor growth in vivo. Here, we evaluate its targeting mechanism and report that E3 selectively internalizes into cancer cells utilizing a pathway that involves transferrin receptor 1 (TfR 1). E3 binds to recombinant human TfR 1 with high affinity and competes with transferrin (Tf) for binding to TfR1. In addition, knockdown or knockin of human TfR1 results in a decrease or increase in E3 cell binding. Here, we reported a molecular model of E3 binding to the transferrin receptor that summarizes our findings.
    Language English
    Publishing date 2023-04-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15082301
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  9. Article ; Online: Protocol for purification of cells in their native state using reversible aptamer-antidote pairs

    Martin D. Requena / Bethany Powell Gray / Bruce A. Sullenger

    STAR Protocols, Vol 4, Iss 3, Pp 102348- (2023)

    2023  

    Abstract: Summary: Cell isolation from complex mixtures is a key step in many clinical and research applications, but standard isolation methods may affect the cell’s biology and are difficult to reverse. Here, we present a method to isolate and restore cells to ... ...

    Abstract Summary: Cell isolation from complex mixtures is a key step in many clinical and research applications, but standard isolation methods may affect the cell’s biology and are difficult to reverse. Here, we present a method to isolate and restore cells to their native state using an aptamer that binds epidermal growth factor receptor (EGFR+)cells and a complementary antisense oligonucleotide to reverse binding.For complete details on the use and execution of this protocol, please refer to Gray et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
    Keywords Cell Biology ; Cell isolation ; Molecular/Chemical Probes ; Biotechnology and bioengineering ; Science (General) ; Q1-390
    Language English
    Publishing date 2023-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: MicroRNA let-7b enhances spinal cord nociceptive synaptic transmission and induces acute and persistent pain through neuronal and microglial signaling.

    Chen, Ouyang / Jiang, Changyu / Berta, Temugin / Powell Gray, Bethany / Furutani, Kenta / Sullenger, Bruce A / Ji, Ru-Rong

    Pain

    2024  

    Abstract: Abstract: Secreted microRNAs (miRNAs) have been detected in various body fluids including the cerebrospinal fluid, yet their direct role in regulating synaptic transmission remains uncertain. We found that intrathecal injection of low dose of let-7b (1 ... ...

    Abstract Abstract: Secreted microRNAs (miRNAs) have been detected in various body fluids including the cerebrospinal fluid, yet their direct role in regulating synaptic transmission remains uncertain. We found that intrathecal injection of low dose of let-7b (1 μg) induced short-term (<24 hours) mechanical allodynia and heat hyperalgesia, a response that is compromised in Tlr7-/- or Trpa1-/- mice. Ex vivo and in vivo calcium imaging in GCaMP6-report mice revealed increased calcium signal in spinal cord afferent terminals and doral root ganglion/dorsal root ganglia neurons following spinal perfusion and intraplantar injection of let-7b. Patch-clamp recordings also demonstrated enhanced excitatory synaptic transmission (miniature excitatory postsynaptic currents [EPSCs]) in spinal nociceptive neurons following let-7b perfusion or optogenetic activation of axonal terminals. The elevation in spinal calcium signaling and EPSCs was dependent on the presence of toll-like receptor-7 (TLR7) and transient receptor potential ion channel subtype A1 (TRPA1). In addition, endogenous let-7b is enriched in spinal cord synaptosome, and peripheral inflammation increased let-7b in doral root ganglion/dorsal root ganglia neurons, spinal cord tissue, and the cerebrospinal fluid. Notably, let-7b antagomir inhibited inflammatory pain and inflammation-induced synaptic plasticity (EPSC increase), suggesting an endogenous role of let-7b in regulating pain and synaptic transmission. Furthermore, intrathecal injection of let-7b, at a higher dose (10 μg), induced persistent mechanical allodynia for >2 weeks, which was abolished in Tlr7-/- mice. The high dose of let-7b also induced microgliosis in the spinal cord. Of interest, intrathecal minocycline only inhibited let-7b-induced mechanical allodynia in male but not female mice. Our findings indicate that the secreted microRNA let-7b has the capacity to provoke pain through both neuronal and glial signaling, thereby establishing miRNA as an emerging neuromodulator.
    Language English
    Publishing date 2024-03-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 193153-2
    ISSN 1872-6623 ; 0304-3959
    ISSN (online) 1872-6623
    ISSN 0304-3959
    DOI 10.1097/j.pain.0000000000003206
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