Pub Date : 2022-04-19DOI: 10.1080/0377919X.2022.2040323
Fatima Aamir
Abstract This article explores both the collapse of Palestinian futurity and practices of alternative meaning making in Adania Shibli’s novel Minor Detail. Through her unique negotiation with Palestinian literary modernism, including her defamiliarizing engagement of realist aesthetics within the text, as well as the defining role she assigns Israeli settler colonialism in producing modernist alienation, Shibli troubles historical truth and avoids the close-ended museumification of events. Despite the collapse of Palestinian futurity within the text, Shibli’s literary experimentation creates gaps not only in the totalizing nature of Israeli occupation, but also in its historical hegemony, reflecting the practice of what Ariella Azoulay terms “potential history.” While Shibli’s stuttering and irrational Palestinian narrator, as well as the ambiguous nature of her narrative form, might not reflect straightforward resistance to settler-colonial totality, they unsettle historical narrative from within and open up new ways to consider truth and meaning.
{"title":"Palestinian Modernism: Meaning Making and Alternative Historical Practices in Adania Shibli’s Minor Detail","authors":"Fatima Aamir","doi":"10.1080/0377919X.2022.2040323","DOIUrl":"https://doi.org/10.1080/0377919X.2022.2040323","url":null,"abstract":"Abstract This article explores both the collapse of Palestinian futurity and practices of alternative meaning making in Adania Shibli’s novel Minor Detail. Through her unique negotiation with Palestinian literary modernism, including her defamiliarizing engagement of realist aesthetics within the text, as well as the defining role she assigns Israeli settler colonialism in producing modernist alienation, Shibli troubles historical truth and avoids the close-ended museumification of events. Despite the collapse of Palestinian futurity within the text, Shibli’s literary experimentation creates gaps not only in the totalizing nature of Israeli occupation, but also in its historical hegemony, reflecting the practice of what Ariella Azoulay terms “potential history.” While Shibli’s stuttering and irrational Palestinian narrator, as well as the ambiguous nature of her narrative form, might not reflect straightforward resistance to settler-colonial totality, they unsettle historical narrative from within and open up new ways to consider truth and meaning.","PeriodicalId":46375,"journal":{"name":"Journal of Palestine Studies","volume":"51 1","pages":"27 - 42"},"PeriodicalIF":0.8,"publicationDate":"2022-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47672522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"社会学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-19DOI: 10.1080/0377919X.2022.2040325
Lyndall Herman
ideologically. What stood between the PFLP and such an achievement, we learn, was the pan-Arab ideological background of its founding leadership, the limited theoretical capacities of its secretary-general, George Habash, and its rigid organizational structure. The book’s narrative fails to highlight these factors and their role in the PFLP’s dilemma. Leopardi’s contribution lies in framing and giving an overview of the PFLP’s conduct between 1982–2007. The concepts Leopardi utilizes, such as “opposition-integration dilemma,” demonstrate analytical potential for the study of the Palestinian Left and opposition movements in general. At a time when unity is invoked as a solution to the Palestinian “impasse,” Leopardi’s argument that the pursuit of unity both reflected and contributed to the PFLP’s marginality provides a critical perspective worth considering. Furthermore, Leopardi presents fruitful avenues for future research—such as his brief comparison of the Palestinian and Kurdish Left. For these reasons, and despite its shortcomings, this book is a welcome addition to studies of the PRM and the Palestinian Left specifically.
{"title":"A History of Palestinian Islamic Jihad: Faith, Awareness, and Revolution in the Middle East","authors":"Lyndall Herman","doi":"10.1080/0377919X.2022.2040325","DOIUrl":"https://doi.org/10.1080/0377919X.2022.2040325","url":null,"abstract":"ideologically. What stood between the PFLP and such an achievement, we learn, was the pan-Arab ideological background of its founding leadership, the limited theoretical capacities of its secretary-general, George Habash, and its rigid organizational structure. The book’s narrative fails to highlight these factors and their role in the PFLP’s dilemma. Leopardi’s contribution lies in framing and giving an overview of the PFLP’s conduct between 1982–2007. The concepts Leopardi utilizes, such as “opposition-integration dilemma,” demonstrate analytical potential for the study of the Palestinian Left and opposition movements in general. At a time when unity is invoked as a solution to the Palestinian “impasse,” Leopardi’s argument that the pursuit of unity both reflected and contributed to the PFLP’s marginality provides a critical perspective worth considering. Furthermore, Leopardi presents fruitful avenues for future research—such as his brief comparison of the Palestinian and Kurdish Left. For these reasons, and despite its shortcomings, this book is a welcome addition to studies of the PRM and the Palestinian Left specifically.","PeriodicalId":46375,"journal":{"name":"Journal of Palestine Studies","volume":"51 1","pages":"79 - 80"},"PeriodicalIF":0.8,"publicationDate":"2022-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42438495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"社会学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-13DOI: 10.1080/0377919X.2022.2040881
Samirah Alkassim
In this slim and affordable book, Anandi Ramamurthy and Paul Kelemen write with authority from their respective engagements as professors, curators, and activists. Struggling to Be Seen: The Travails of Palestinian Cinema educates newcomers to the Palestinian struggle, but it can also be appreciated by the Palestine-solidarity base for its concise overview of the challenges, past and present, characterizing Palestinian cinema. As such, it delivers the objectives of its publisher, Daraja Press, in creating cultures of solidarity and supporting emancipatory struggles of oppressed people across the world. Relying on primary documents and field-based methodology, this book offers an accessible primer for undergraduate and graduate classes, as well as the general public. It consists of an introduction, six short chapters, a conclusion, and twenty pages of back matter, including a filmography and four appendices that provide colorful visual documentations corresponding to the chapters. Across these components, the authors identify essential issues and challenges from production to exhibition and reception, key figures and texts, and recommended films. In so doing, they situate the creation and sustenance of Palestinian cinema as crucial to countering the erasure of Palestine, particularly when screened within Western cultural centers. They frame their book as the outcome of collaborative research conducted with Palestinian film organizations and British cultural organizations to examine the programming of Palestinian cinema in the UK, which they offer as potentially instructive to such programming in other countries. This comparison is clarified in the chapters described below. The book skims the history of Palestinian filmmaking (chapter 1, pp. 7–12), presenting examples of contemporary resistance through collective endeavors focused on building film culture in Palestine. It follows organizations like Filmlab in Ramallah (chapter 2, pp. 13–19), Dar al-Kalima University College of Arts and Culture in Bethlehem, and the Palestine Film Institute in Jerusalem (chapter 1) to demonstrate the continuity of Palestinian cinema despite the challenges created by the political impasse of the Israeli occupation. The authors’ main concern with the preservation of Palestinian cinema is evidenced (chapter 3, pp. 20–28) in the experience they recount of restoring five revolutionary films held in private collections, to commemorate the seventieth anniversary of the Nakba. They provide short analyses of several films, both fiction and documentary (chapter 4, pp. 29–35), that exemplify the difficulties of checkpoints, borders, exile, and displacement that have asserted their thematic significance in Palestinian cinema. They note (chapter 5, pp. 36–42) the increasing number of Palestinian filmmakers since the early 2000s and discuss the necessity of creating spaces and opportunities to see their films while trying to reach wider audiences beyond the base. Lastly, they add
{"title":"Struggling to Be Seen: The Travails of Palestinian Cinema","authors":"Samirah Alkassim","doi":"10.1080/0377919X.2022.2040881","DOIUrl":"https://doi.org/10.1080/0377919X.2022.2040881","url":null,"abstract":"In this slim and affordable book, Anandi Ramamurthy and Paul Kelemen write with authority from their respective engagements as professors, curators, and activists. Struggling to Be Seen: The Travails of Palestinian Cinema educates newcomers to the Palestinian struggle, but it can also be appreciated by the Palestine-solidarity base for its concise overview of the challenges, past and present, characterizing Palestinian cinema. As such, it delivers the objectives of its publisher, Daraja Press, in creating cultures of solidarity and supporting emancipatory struggles of oppressed people across the world. Relying on primary documents and field-based methodology, this book offers an accessible primer for undergraduate and graduate classes, as well as the general public. It consists of an introduction, six short chapters, a conclusion, and twenty pages of back matter, including a filmography and four appendices that provide colorful visual documentations corresponding to the chapters. Across these components, the authors identify essential issues and challenges from production to exhibition and reception, key figures and texts, and recommended films. In so doing, they situate the creation and sustenance of Palestinian cinema as crucial to countering the erasure of Palestine, particularly when screened within Western cultural centers. They frame their book as the outcome of collaborative research conducted with Palestinian film organizations and British cultural organizations to examine the programming of Palestinian cinema in the UK, which they offer as potentially instructive to such programming in other countries. This comparison is clarified in the chapters described below. The book skims the history of Palestinian filmmaking (chapter 1, pp. 7–12), presenting examples of contemporary resistance through collective endeavors focused on building film culture in Palestine. It follows organizations like Filmlab in Ramallah (chapter 2, pp. 13–19), Dar al-Kalima University College of Arts and Culture in Bethlehem, and the Palestine Film Institute in Jerusalem (chapter 1) to demonstrate the continuity of Palestinian cinema despite the challenges created by the political impasse of the Israeli occupation. The authors’ main concern with the preservation of Palestinian cinema is evidenced (chapter 3, pp. 20–28) in the experience they recount of restoring five revolutionary films held in private collections, to commemorate the seventieth anniversary of the Nakba. They provide short analyses of several films, both fiction and documentary (chapter 4, pp. 29–35), that exemplify the difficulties of checkpoints, borders, exile, and displacement that have asserted their thematic significance in Palestinian cinema. They note (chapter 5, pp. 36–42) the increasing number of Palestinian filmmakers since the early 2000s and discuss the necessity of creating spaces and opportunities to see their films while trying to reach wider audiences beyond the base. Lastly, they add","PeriodicalId":46375,"journal":{"name":"Journal of Palestine Studies","volume":"12 2","pages":"76 - 77"},"PeriodicalIF":0.8,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41269460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"社会学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-13DOI: 10.1080/0377919X.2022.2050630
S. Seikaly
Abstract In this article, coeditor Sherene Seikaly examines the Journal of Palestine Studies’ first two decades as the premier English-language academic publication on the Palestinian question and what was once referred to as the Arab-Israeli conflict. Using the keyword “war” in article titles as a prism for a granular analysis of the knowledge produced in the Journal, Seikaly traces some of the trends that undergirded JPS’s evolution—its prescriptive, programmatic, and prognosticating approach that was deeply imbricated in the patriarchal paradigms of international relations and political science (Revolution with a capital “R,” the “great men” of history, the imperative to make one’s case before the colonizer), but also a capacious space to view the contested terrain of knowledge production. A close reading of seventeen articles and one interview over the arc of twenty years illuminates the Journal’s pivotal role as a repository of primary and secondary literature and as an archive of Palestine and the Palestinians.
{"title":"In the Shadow of War: The Journal of Palestine Studies as Archive","authors":"S. Seikaly","doi":"10.1080/0377919X.2022.2050630","DOIUrl":"https://doi.org/10.1080/0377919X.2022.2050630","url":null,"abstract":"Abstract In this article, coeditor Sherene Seikaly examines the Journal of Palestine Studies’ first two decades as the premier English-language academic publication on the Palestinian question and what was once referred to as the Arab-Israeli conflict. Using the keyword “war” in article titles as a prism for a granular analysis of the knowledge produced in the Journal, Seikaly traces some of the trends that undergirded JPS’s evolution—its prescriptive, programmatic, and prognosticating approach that was deeply imbricated in the patriarchal paradigms of international relations and political science (Revolution with a capital “R,” the “great men” of history, the imperative to make one’s case before the colonizer), but also a capacious space to view the contested terrain of knowledge production. A close reading of seventeen articles and one interview over the arc of twenty years illuminates the Journal’s pivotal role as a repository of primary and secondary literature and as an archive of Palestine and the Palestinians.","PeriodicalId":46375,"journal":{"name":"Journal of Palestine Studies","volume":"51 1","pages":"5 - 26"},"PeriodicalIF":0.8,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48703238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"社会学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-13DOI: 10.1080/0377919x.2022.2044184
L. Lambert
Abstract In this essay, architect-activist and Funambulist editor-in-chief Léopold Lambert reflects on the ways that the architectural profession can be, and historically has been, complicit in structural injustice. He ties together the seemingly unrelated deaths of two men, uncovering in the process how architecture consecrates, amplifies, or abets oppression, be it in the settler-colonial context of occupied Palestine, in the French criminal justice system, or in the historical framework of the transatlantic slave trade.
{"title":"Two Deaths: A Reflection on Architecture, Carcerality, and Palestine","authors":"L. Lambert","doi":"10.1080/0377919x.2022.2044184","DOIUrl":"https://doi.org/10.1080/0377919x.2022.2044184","url":null,"abstract":"Abstract In this essay, architect-activist and Funambulist editor-in-chief Léopold Lambert reflects on the ways that the architectural profession can be, and historically has been, complicit in structural injustice. He ties together the seemingly unrelated deaths of two men, uncovering in the process how architecture consecrates, amplifies, or abets oppression, be it in the settler-colonial context of occupied Palestine, in the French criminal justice system, or in the historical framework of the transatlantic slave trade.","PeriodicalId":46375,"journal":{"name":"Journal of Palestine Studies","volume":"51 1","pages":"62 - 65"},"PeriodicalIF":0.8,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41778798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"社会学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-13DOI: 10.1080/0377919X.2022.2040331
Faiq Mari
describe their challenges and successes in curating a program of short films in the UK as part of the seventieth anniversary of the Nakba in collaboration with the Sheffield Palestine Cultural Exchange, a cultural organization. They discuss their success in attracting a wider audience by programming around the universal theme of love, which allowed for reflection on the different types of love that connect to the usurpation of Palestinian land, the history of ethnic cleansing, and life under occupation. Perhaps it is unfortunate that facts and the systemic racism supporting Israeli settler-colonial occupation are not always enough to command the attention of mainstream audiences, but that is precisely why accessible books like this are so valuable. It is the perfect companion for a focused Palestine-themed film screening, series, or festival, where the aim is not only to reach the base of supporters in celebration of Palestinian and Arab cinema but to educate a wider audience about the ongoing struggles faced by Palestinians as demonstrated through their films. The authors conclude by optimistically observing that the achievements of Palestinian cinema “are enduring and signal a growing international sympathy” for the Palestinian cause (p. 54), despite the intensified precarity for Palestinian cinema and solidarity activism. While the histories of this subject are more deeply analyzed elsewhere, the authors provide an encounter that invites research, collaboration, and involvement, modeling the activity of building film culture as a contemporary means of advancing justice for Palestine.
{"title":"The Palestinian Left and Its Decline: Loyal Opposition","authors":"Faiq Mari","doi":"10.1080/0377919X.2022.2040331","DOIUrl":"https://doi.org/10.1080/0377919X.2022.2040331","url":null,"abstract":"describe their challenges and successes in curating a program of short films in the UK as part of the seventieth anniversary of the Nakba in collaboration with the Sheffield Palestine Cultural Exchange, a cultural organization. They discuss their success in attracting a wider audience by programming around the universal theme of love, which allowed for reflection on the different types of love that connect to the usurpation of Palestinian land, the history of ethnic cleansing, and life under occupation. Perhaps it is unfortunate that facts and the systemic racism supporting Israeli settler-colonial occupation are not always enough to command the attention of mainstream audiences, but that is precisely why accessible books like this are so valuable. It is the perfect companion for a focused Palestine-themed film screening, series, or festival, where the aim is not only to reach the base of supporters in celebration of Palestinian and Arab cinema but to educate a wider audience about the ongoing struggles faced by Palestinians as demonstrated through their films. The authors conclude by optimistically observing that the achievements of Palestinian cinema “are enduring and signal a growing international sympathy” for the Palestinian cause (p. 54), despite the intensified precarity for Palestinian cinema and solidarity activism. While the histories of this subject are more deeply analyzed elsewhere, the authors provide an encounter that invites research, collaboration, and involvement, modeling the activity of building film culture as a contemporary means of advancing justice for Palestine.","PeriodicalId":46375,"journal":{"name":"Journal of Palestine Studies","volume":"51 1","pages":"77 - 79"},"PeriodicalIF":0.8,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41431304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"社会学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-13DOI: 10.1080/0377919x.2022.2040880
Diana Buttu
Abstract Israel has long sought to erase Palestinians, Palestinian resistance, and Palestinian organizations. In Israel’s latest rendition of erasure, Palestinian nongovernmental organizations (NGOs) have become the new target. By labeling NGO staff, and now NGOs, as “terror-affiliated,” Israel is attempting to silence these organizations by making it impossible for them to be funded. Looking at the case of Mohammed El Halabi from World Vision, one can see that it does not take much for donors to run scared: just using the “t” word is sufficient, with no need for evidence.
长期以来，以色列一直试图消灭巴勒斯坦人、巴勒斯坦抵抗组织和巴勒斯坦组织。在以色列最新的“抹除”行动中，巴勒斯坦非政府组织(ngo)成为了新的目标。通过给非政府组织的工作人员贴上“与恐怖分子有关联”的标签，以色列正试图通过使这些组织无法获得资助来沉默这些组织。看看世界宣明会(World Vision)的穆罕默德·哈拉比(Mohammed El Halabi)的案例，人们就会发现，捐赠者不需要太多就会感到害怕:只要用“t”这个词就足够了，不需要证据。
{"title":"How to Crush Palestinian NGOs: Just Use the “T” Word","authors":"Diana Buttu","doi":"10.1080/0377919x.2022.2040880","DOIUrl":"https://doi.org/10.1080/0377919x.2022.2040880","url":null,"abstract":"Abstract Israel has long sought to erase Palestinians, Palestinian resistance, and Palestinian organizations. In Israel’s latest rendition of erasure, Palestinian nongovernmental organizations (NGOs) have become the new target. By labeling NGO staff, and now NGOs, as “terror-affiliated,” Israel is attempting to silence these organizations by making it impossible for them to be funded. Looking at the case of Mohammed El Halabi from World Vision, one can see that it does not take much for donors to run scared: just using the “t” word is sufficient, with no need for evidence.","PeriodicalId":46375,"journal":{"name":"Journal of Palestine Studies","volume":"51 1","pages":"57 - 61"},"PeriodicalIF":0.8,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48432730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"社会学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-11DOI: 10.1080/0377919x.2022.2043136
Marya Farah
{"title":"Al-Haq: A Global History of the First Palestinian Human Rights Organization","authors":"Marya Farah","doi":"10.1080/0377919x.2022.2043136","DOIUrl":"https://doi.org/10.1080/0377919x.2022.2043136","url":null,"abstract":"","PeriodicalId":46375,"journal":{"name":"Journal of Palestine Studies","volume":"51 1","pages":"72 - 73"},"PeriodicalIF":0.8,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47326488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"社会学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-11DOI: 10.1080/0377919x.2022.2040883
N. Perugini
{"title":"A History of False Hope: Investigative Commissions in Palestine","authors":"N. Perugini","doi":"10.1080/0377919x.2022.2040883","DOIUrl":"https://doi.org/10.1080/0377919x.2022.2040883","url":null,"abstract":"","PeriodicalId":46375,"journal":{"name":"Journal of Palestine Studies","volume":"51 1","pages":"74 - 75"},"PeriodicalIF":0.8,"publicationDate":"2022-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46713121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"社会学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-16eCollection Date: 2022-06-09DOI: 10.1016/j.omtm.2022.03.008
Alicia Davis, Kevin V Morris, Galina Shevchenko
Hypoxia is a characteristic feature of solid tumors that contributes to tumor aggressiveness and is associated with resistance to cancer therapy. The hypoxia inducible factor-1 (HIF-1) transcription factor complex mediates hypoxia-specific gene expression by binding to hypoxia-responsive element (HRE) sequences within the promoter of target genes. HRE-driven expression of therapeutic cargo has been widely explored as a strategy to achieve cancer-specific gene expression. By utilizing this system, we achieve hypoxia-specific expression of two therapeutically relevant cargo elements: the herpes simplex virus thymidine kinase (HSV-tk) suicide gene and the CRISPR-Cas9 nuclease. Using an expression vector containing five copies of the HRE derived from the vascular endothelial growth factor gene, we are able to show high transgene expression in cells in a hypoxic environment, similar to levels achieved using the cytomegalovirus (CMV) and CBh promoters. Furthermore, we are able to deliver our therapeutic cargo to tumor cells with high efficiency using plasmid-packaged lipid nanoparticles (LNPs) to achieve specific killing of tumor cells in hypoxic conditions while maintaining tight regulation with no significant changes to cell viability in normoxia.
缺氧是实体瘤的一个特征，它有助于提高肿瘤的侵袭性，并与癌症治疗的抗药性有关。低氧诱导因子-1（HIF-1）转录因子复合物通过与靶基因启动子内的低氧反应元件（HRE）序列结合，介导低氧特异性基因表达。作为一种实现癌症特异性基因表达的策略，HRE 驱动的治疗药物表达已被广泛探索。通过利用这一系统，我们实现了两种治疗相关载体的缺氧特异性表达：单纯疱疹病毒胸苷激酶（HSV-tk）自杀基因和 CRISPR-Cas9 核酸酶。通过使用一种含有五个来自血管内皮生长因子基因的 HRE 拷贝的表达载体，我们能够在缺氧环境下的细胞中显示出较高的转基因表达量，与使用巨细胞病毒 (CMV) 和 CBh 启动子达到的水平类似。此外，我们还能利用质粒包装的脂质纳米颗粒（LNPs）将治疗药物高效地输送到肿瘤细胞中，从而实现在缺氧条件下对肿瘤细胞的特异性杀伤，同时在常氧条件下保持严格的调控，细胞存活率不会发生显著变化。
{"title":"Hypoxia-directed tumor targeting of CRISPR-Cas9 and HSV-TK suicide gene therapy using lipid nanoparticles.","authors":"Alicia Davis, Kevin V Morris, Galina Shevchenko","doi":"10.1016/j.omtm.2022.03.008","DOIUrl":"10.1016/j.omtm.2022.03.008","url":null,"abstract":"<p><p>Hypoxia is a characteristic feature of solid tumors that contributes to tumor aggressiveness and is associated with resistance to cancer therapy. The hypoxia inducible factor-1 (HIF-1) transcription factor complex mediates hypoxia-specific gene expression by binding to hypoxia-responsive element (HRE) sequences within the promoter of target genes. HRE-driven expression of therapeutic cargo has been widely explored as a strategy to achieve cancer-specific gene expression. By utilizing this system, we achieve hypoxia-specific expression of two therapeutically relevant cargo elements: the herpes simplex virus thymidine kinase (HSV-tk) suicide gene and the CRISPR-Cas9 nuclease. Using an expression vector containing five copies of the HRE derived from the vascular endothelial growth factor gene, we are able to show high transgene expression in cells in a hypoxic environment, similar to levels achieved using the cytomegalovirus (CMV) and CBh promoters. Furthermore, we are able to deliver our therapeutic cargo to tumor cells with high efficiency using plasmid-packaged lipid nanoparticles (LNPs) to achieve specific killing of tumor cells in hypoxic conditions while maintaining tight regulation with no significant changes to cell viability in normoxia.</p>","PeriodicalId":46375,"journal":{"name":"Journal of Palestine Studies","volume":"31 1","pages":"158-169"},"PeriodicalIF":4.7,"publicationDate":"2022-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89399437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"社会学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：