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  1. Article ; Online: Computational analysis of cas proteins unlocks new potential in HIV-1 targeted gene therapy.

    Dampier, Will / Berman, Rachel / Nonnemacher, Michael R / Wigdahl, Brian

    Frontiers in genome editing

    2024  Volume 5, Page(s) 1248982

    Abstract: Introduction: ...

    Abstract Introduction:
    Language English
    Publishing date 2024-01-04
    Publishing country Switzerland
    Document type Journal Article
    ISSN 2673-3439
    ISSN (online) 2673-3439
    DOI 10.3389/fgeed.2023.1248982
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: What's in a cure: designing a broad-spectrum HIV gene therapy.

    Berman, Rachel E / Dampier, Will / Nonnemacher, Michael R / Wigdahl, Brian

    Current opinion in HIV and AIDS

    2024  Volume 19, Issue 3, Page(s) 150–156

    Abstract: Purpose of review: The leading gene editing strategy for a human immunodeficiency virus type 1 (HIV-1) cure involves the delivery of SaCas9 and two guide RNAs (gRNAs) in an adeno-associated viral (AAV) vector. As a dual-component system, CRISPR is ... ...

    Abstract Purpose of review: The leading gene editing strategy for a human immunodeficiency virus type 1 (HIV-1) cure involves the delivery of SaCas9 and two guide RNAs (gRNAs) in an adeno-associated viral (AAV) vector. As a dual-component system, CRISPR is targeted to a genetic locus through the choice of a Cas effector and gRNA protospacer design pair. As CRISPR research has expanded in recent years, these components have been investigated for utilization in cure strategies, which will be discussed in this article.
    Recent findings: Type II SpCas9 and SaCas9 have been the leading Cas effectors across gene editing therapeutics to date. Additionally, extensive research has expanded the potential to multiplex gRNAs and target them effectively to the highly genetically diverse HIV-1 provirus. More recently, the Type V family of Cas12 effectors opens a new opportunity to use a smaller Cas protein for packaging into an AAV vector with multiplexed gRNAs.
    Summary: In understanding the individual components of a CRISPR/Cas therapeutic cure for HIV-1, it is important to know that the currently used strategies can be improved upon. Future areas will include alternative smaller Cas effectors, multiplexed gRNAs designs, and/or alternative delivery modalities.
    MeSH term(s) Humans ; CRISPR-Cas Systems ; RNA, Guide, CRISPR-Cas Systems ; HIV Infections ; Gene Editing ; HIV-1/genetics ; Genetic Therapy
    Chemical Substances RNA, Guide, CRISPR-Cas Systems
    Language English
    Publishing date 2024-03-01
    Publishing country United States
    Document type Review ; Journal Article
    ZDB-ID 2502511-9
    ISSN 1746-6318 ; 1746-630X
    ISSN (online) 1746-6318
    ISSN 1746-630X
    DOI 10.1097/COH.0000000000000846
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Commentary to Gusenbauer and Haddaway 2020: Evaluating retrieval qualities of Google Scholar and PubMed.

    Klopfenstein, D V / Dampier, Will

    Research synthesis methods

    2020  Volume 12, Issue 2, Page(s) 126–135

    Abstract: We read with considerable interest the study by Gusenbauer and Haddaway (Gusenbauer and Haddaway, 2020, Research Synthesis Methods, doi:10.1002/jrsm.1378) comparing the systematic search qualities of 28 search systems, including Google Scholar (GS) and ... ...

    Abstract We read with considerable interest the study by Gusenbauer and Haddaway (Gusenbauer and Haddaway, 2020, Research Synthesis Methods, doi:10.1002/jrsm.1378) comparing the systematic search qualities of 28 search systems, including Google Scholar (GS) and PubMed. Google Scholar and PubMed are the two most popular free academic search tools in biology and chemistry, with GS being the number one search tool in the world. Those academics using GS as their principal system for literature searches may be unaware of research which enumerates five critical features for scientific literature tools that greatly influenced Gusenbauer's 2020 study. Using this list as the framework for a targeted comparison between just GS and PubMed, we found stark differences which overwhelmingly favored PubMed. In this comment, we show that by comparing the characteristics of the two search tools, features that are particularly useful in one search tool, but are missing in the other, are strikingly spotlighted. One especially popular feature that ubiquitously appears in GS, but not in PubMed, is the forward citation search found under every citation as a clickable Cited by N link. We seek to improve the PubMed search experience using two approaches. First, we request that PubMed add Cited by N links, making them as omnipresent as the GS links. Second, we created an open-source command-line tool, pmidcite, which is used alongside PubMed to give information to researchers to help with the choice of the next paper to examine, analogous to how GS's Cited by N links help to guide users. Find pmidcite at https://github.com/dvklopfenstein/pmidcite.
    MeSH term(s) Data Accuracy ; PubMed ; Publications ; Research Design ; Search Engine
    Language English
    Publishing date 2020-10-08
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 2548499-0
    ISSN 1759-2887 ; 1759-2879
    ISSN (online) 1759-2887
    ISSN 1759-2879
    DOI 10.1002/jrsm.1456
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  4. Article: Immunomodulatory Effects of Non-Thermal Plasma in a Model for Latent HIV-1 Infection: Implications for an HIV-1-Specific Immunotherapy.

    Mohamed, Hager / Berman, Rachel / Connors, Jennifer / Haddad, Elias K / Miller, Vandana / Nonnemacher, Michael R / Dampier, Will / Wigdahl, Brian / Krebs, Fred C

    Biomedicines

    2023  Volume 11, Issue 1

    Abstract: In people living with HIV-1 (PLWH), antiretroviral therapy (ART) eventually becomes necessary to suppress the emergence of human immunodeficiency virus type 1 (HIV-1) replication from latent reservoirs because HIV-1-specific immune responses in PLWH are ... ...

    Abstract In people living with HIV-1 (PLWH), antiretroviral therapy (ART) eventually becomes necessary to suppress the emergence of human immunodeficiency virus type 1 (HIV-1) replication from latent reservoirs because HIV-1-specific immune responses in PLWH are suboptimal. Immunotherapies that enhance anti-HIV-1 immune responses for better control of virus reemergence from latent reservoirs are postulated to offer ART-free control of HIV-1. Toward the goal of developing an HIV-1-specific immunotherapy based on non-thermal plasma (NTP), the early immunological responses to NTP-exposed latently infected T lymphocytes were examined. Application of NTP to the J-Lat T-lymphocyte cell line (clones 10.6 and 15.4) stimulated monocyte recruitment and macrophage maturation, which are key steps in initiation of an immune response. In contrast, CD8+ T lymphocytes in a mixed lymphocyte reaction assay were not stimulated by the presence of NTP-exposed J-Lat cells. Furthermore, co-culture of NTP-exposed J-Lat cells with mature phagocytes did not modulate their antigen presentation to primary CD8+ T lymphocytes (cross-presentation). However, reactivation from latency was stimulated in a clone-specific manner by NTP. Overall, these studies, which demonstrated that ex vivo application of NTP to latently infected lymphocytes can stimulate key immune cell responses, advance the development of an NTP-based immunotherapy that will provide ART-free control of HIV-1 reactivation in PLWH.
    Language English
    Publishing date 2023-01-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720867-9
    ISSN 2227-9059
    ISSN 2227-9059
    DOI 10.3390/biomedicines11010122
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  5. Article ; Online: HIV-1 cure strategies: why CRISPR?

    Atkins, Andrew J / Allen, Alexander G / Dampier, Will / Haddad, Elias K / Nonnemacher, Michael R / Wigdahl, Brian

    Expert opinion on biological therapy

    2021  Volume 21, Issue 6, Page(s) 781–793

    Abstract: Introduction: Antiretroviral therapy (ART) has transformed prognoses for HIV-1-infected individuals but requires lifelong adherence to prevent viral resurgence. Targeted elimination or permanent deactivation of the latently infected reservoir harboring ... ...

    Abstract Introduction: Antiretroviral therapy (ART) has transformed prognoses for HIV-1-infected individuals but requires lifelong adherence to prevent viral resurgence. Targeted elimination or permanent deactivation of the latently infected reservoir harboring integrated proviral DNA, which drives viral rebound, is a major focus of HIV-1 research.
    Areas covered: This review covers the current approaches to developing curative strategies for HIV-1 that target the latent reservoir. Discussed herein are shock and kill, broadly neutralizing antibodies (bNAbs), block and lock, Chimeric antigen receptor (CAR) T cells, immune checkpoint modulation, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) coreceptor ablation, and CRISPR/Cas9 proviral excision. Emphasis is placed on CRISPR/Cas9 proviral excision/inactivation. Recent advances and future directions toward discovery and translation of HIV-1 therapeutics are discussed.
    Expert opinion: CRISPR/Cas9 proviral targeting fills a niche amongst HIV-1 cure strategies by directly targeting the integrated provirus without the necessity of an innate or adaptive immune response. Each strategy discussed in this review has shown promising results with the potential to yield curative or adjuvant therapies. CRISPR/Cas9 is singular among these in that it addresses the root of the problem, integrated proviral DNA, with the capacity to permanently remove or deactivate the source of HIV-1 recrudescence.
    MeSH term(s) CRISPR-Cas Systems ; HIV Infections/drug therapy ; HIV-1/genetics ; Humans ; Proviruses ; Virus Activation
    Language English
    Publishing date 2021-02-07
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2052501-1
    ISSN 1744-7682 ; 1471-2598
    ISSN (online) 1744-7682
    ISSN 1471-2598
    DOI 10.1080/14712598.2021.1865302
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 6094: Show issues Location:
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    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

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  6. Article ; Online: Prediction of Human Immunodeficiency Virus Type 1 Subtype-Specific Off-Target Effects Arising from CRISPR-Cas9 Gene Editing Therapy.

    Link, Robert W / Nonnemacher, Michael R / Wigdahl, Brian / Dampier, Will

    The CRISPR journal

    2019  Volume 1, Page(s) 294–302

    Abstract: Chronic human immunodeficiency virus type 1 (HIV-1) disease is characterized by the retention of provirus within latently infected cells. Anti-HIV-1 CRISPR-Cas9 gene editing is an attractive strategy to excise or inactivate the HIV-1 genome. Recent ... ...

    Abstract Chronic human immunodeficiency virus type 1 (HIV-1) disease is characterized by the retention of provirus within latently infected cells. Anti-HIV-1 CRISPR-Cas9 gene editing is an attractive strategy to excise or inactivate the HIV-1 genome. Recent strategies have focused on designing gRNAs that target the long terminal repeat (LTR) because 5' and 3' LTR symmetry can facilitate proviral excision. However, the promiscuity of CRISPR-Cas9 gene editing system necessitates the investigation of potential off-target effects. Here, potential gRNAs designed from HIV-1 phylogenetic subtypes using the CRISPRseek tool were investigated. Across the LTR, it was found that certain regions show higher human homology than others. When using recommended cutoffs, 96.40% of gRNAs were predicted to have no high probability off-target effects. Given this observation, while high-probability off-target effects are a potential danger, they can be avoided with proper gRNA design.
    Language English
    Publishing date 2019-04-25
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3017891-5
    ISSN 2573-1602 ; 2573-1599
    ISSN (online) 2573-1602
    ISSN 2573-1599
    DOI 10.1089/crispr.2018.0020
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  7. Article: HIV-1 Tat Length: Comparative and Functional Considerations.

    Mele, Anthony R / Marino, Jamie / Dampier, Will / Wigdahl, Brian / Nonnemacher, Michael R

    Frontiers in microbiology

    2020  Volume 11, Page(s) 444

    Language English
    Publishing date 2020-03-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2020.00444
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Assessment of anti-HIV-1 guide RNA efficacy in cells containing the viral target sequence, corresponding gRNA, and CRISPR/Cas9.

    Allen, Alexander G / Chung, Cheng-Han / Worrell, Stephen D / Nwaozo, Glad / Madrid, Rebekah / Mele, Anthony R / Dampier, Will / Nonnemacher, Michael R / Wigdahl, Brian

    Frontiers in genome editing

    2023  Volume 5, Page(s) 1101483

    Abstract: The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 gene editing system has been shown to be effective at inhibiting human immunodeficiency virus type 1 (HIV-1). Studies have not consistently used a trackable dual reporter system ... ...

    Abstract The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 gene editing system has been shown to be effective at inhibiting human immunodeficiency virus type 1 (HIV-1). Studies have not consistently used a trackable dual reporter system to determine what cells received the Cas9/gRNA to determine the overall knockdown of HIV. Some studies have used stably transduced cells under drug selection to accomplish this goal. Here a two-color system was used that allows tracking of viral protein expression and which cells received the CRISPR/Cas9 system. These experiments ensured that each gRNA used was a perfect match to the intended target to remove this variable. The data showed that gRNAs targeting the transactivation response element (TAR) region or other highly conserved regions of the HIV-1 genome were effective at stopping viral gene expression, with multiple assays demonstrating greater than 95 percent reduction. Conversely, gRNAs targeting conserved sites of the 5' portion of the U3 region were largely ineffective, demonstrating that the location of edits in the long terminal repeat (LTR) matter with respect to function. In addition, it was observed that a gRNA targeting Tat was effective in a T-cell model of HIV-1 latency. Taken together, these studies demonstrated gRNAs designed to highly conserved functional regions have near 100% efficacy
    Language English
    Publishing date 2023-04-13
    Publishing country Switzerland
    Document type Journal Article
    ISSN 2673-3439
    ISSN (online) 2673-3439
    DOI 10.3389/fgeed.2023.1101483
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  9. Article ; Online: Off-Target Analysis in Gene Editing and Applications for Clinical Translation of CRISPR/Cas9 in HIV-1 Therapy.

    Atkins, Andrew / Chung, Cheng-Han / Allen, Alexander G / Dampier, Will / Gurrola, Theodore E / Sariyer, Ilker K / Nonnemacher, Michael R / Wigdahl, Brian

    Frontiers in genome editing

    2021  Volume 3, Page(s) 673022

    Abstract: As genome-editing nucleases move toward broader clinical applications, the need to define the limits of their specificity and efficiency increases. A variety of approaches for nuclease cleavage detection have been developed, allowing a full-genome survey ...

    Abstract As genome-editing nucleases move toward broader clinical applications, the need to define the limits of their specificity and efficiency increases. A variety of approaches for nuclease cleavage detection have been developed, allowing a full-genome survey of the targeting landscape and the detection of a variety of repair outcomes for nuclease-induced double-strand breaks. Each approach has advantages and disadvantages relating to the means of target-site capture, target enrichment mechanism, cellular environment, false discovery, and validation of bona fide off-target cleavage sites in cells. This review examines the strengths, limitations, and origins of the different classes of off-target cleavage detection systems including anchored primer enrichment (GUIDE-seq),
    Language English
    Publishing date 2021-08-17
    Publishing country Switzerland
    Document type Journal Article ; Review
    ISSN 2673-3439
    ISSN (online) 2673-3439
    DOI 10.3389/fgeed.2021.673022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Computational Design of gRNAs Targeting Genetic Variants Across HIV-1 Subtypes for CRISPR-Mediated Antiviral Therapy.

    Chung, Cheng-Han / Allen, Alexander G / Atkins, Andrew / Link, Robert W / Nonnemacher, Michael R / Dampier, Will / Wigdahl, Brian

    Frontiers in cellular and infection microbiology

    2021  Volume 11, Page(s) 593077

    Abstract: Clustered regularly interspaced short palindromic repeats (CRISPR)-based HIV-1 genome editing has shown promising outcomes ... ...

    Abstract Clustered regularly interspaced short palindromic repeats (CRISPR)-based HIV-1 genome editing has shown promising outcomes in
    MeSH term(s) Antiviral Agents ; CRISPR-Cas Systems ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Genome, Viral ; HIV-1/genetics ; Humans ; RNA, Guide, CRISPR-Cas Systems/genetics
    Chemical Substances Antiviral Agents ; RNA, Guide, CRISPR-Cas Systems
    Language English
    Publishing date 2021-03-09
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2619676-1
    ISSN 2235-2988 ; 2235-2988
    ISSN (online) 2235-2988
    ISSN 2235-2988
    DOI 10.3389/fcimb.2021.593077
    Database MEDical Literature Analysis and Retrieval System OnLINE

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