Drugging p53 in cancer: one protein, many targets

Nature Reviews Drug Discovery, Год журнала: 2022, Номер 22(2), С. 127 - 144

Опубликована: Окт. 10, 2022

Язык: Английский

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CRISPR Gene Therapy: Applications, Limitations, and Implications for the Future

Frontiers in Oncology, Год журнала: 2020, Номер 10

Опубликована: Авг. 7, 2020

A series of recent discoveries harnessing the adaptive immune system prokaryotes to perform targeted genome editing is having a transformative influence across biological sciences. The discovery Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) proteins has expanded applications genetic research in thousands labs globe redefining our approach gene therapy. Traditional therapy raised some concerns, as its reliance on viral vector delivery therapeutic transgenes can cause both insertional oncogenesis immunogenic toxicity. By obliviating concerns by traditional therapy, CRISPR technology provides relatively simple efficient alternative for site-specific editing. Although it apparent advantages, CRISPR/Cas9 brings own set limitations which must be addressed safe clinical translation. This review focuses evolution role shifting paradigm. We emerging data trials consider best strategy move forward with this powerful but still new technology.

Язык: Английский

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Non-viral Vectors in Gene Therapy: Recent Development, Challenges, and Prospects

The AAPS Journal, Год журнала: 2021, Номер 23(4)

Опубликована: Июнь 2, 2021

Язык: Английский

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Localized Interleukin-12 for Cancer Immunotherapy

Frontiers in Immunology, Год журнала: 2020, Номер 11

Опубликована: Окт. 15, 2020

Interleukin-12 (IL-12) is a potent, pro-inflammatory type 1 cytokine that has long been studied as potential immunotherapy for cancer. Unfortunately, IL-12's remarkable antitumor efficacy in preclinical models yet to be replicated humans. Early clinical trials the mid-1990's showed systemic delivery of IL-12 incurs unintentional signaling and dose-limiting side effects. Yet, it pleiotropic activity, i.e. its ability engage multiple effector mechanisms reverse tumor-induced immunosuppression, makes such an intriguing therapeutic. The development strategies which maximize tumor microenvironment while minimizing exposure are increasing interest. Diverse systems, from immunocytokine fusions polymeric nanoparticles, have demonstrated robust immunity with reduced adverse events studies. Several localized approaches recently reached stage several more at precipice translation. Taken together, systems supporting renaissance may finally allow this potent fulfill considerable potential. This review begins brief historical account monotherapies describes how went promising new cure ostracized black sheep following on-study deaths. bulk comprehensive developments IL-12-based cancer immunotherapies. Advantages limitations different technologies highlighted. Finally, perspectives on immunotherapies utilized widespread application very near future offered.

Язык: Английский

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The approved gene therapy drugs worldwide: from 1998 to 2019

Biotechnology Advances, Год журнала: 2019, Номер 40, С. 107502 - 107502

Опубликована: Дек. 27, 2019

Язык: Английский

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Polymeric Delivery of Therapeutic Nucleic Acids

Chemical Reviews, Год журнала: 2021, Номер 121(18), С. 11527 - 11652

Опубликована: Май 3, 2021

The advent of genome editing has transformed the therapeutic landscape for several debilitating diseases, and clinical outlook gene therapeutics never been more promising. potential nucleic acids limited by a reliance on engineered viral vectors delivery. Chemically defined polymers can remediate technological, regulatory, challenges associated with modes Because their scalability, versatility, exquisite tunability, are ideal biomaterial platforms delivering acid payloads efficiently while minimizing immune response cellular toxicity. While polymeric delivery progressed significantly in past four decades, translation vehicles faces formidable challenges. aim our Account is to illustrate diverse concepts designing towards meeting goals vivo ex therapy. Here, we highlight classes employed summarize recent work understanding contributions chemical architectural design parameters. We touch upon characterization methods used visualize understand events transpiring at interfaces between polymer, acids, physiological environment. conclude that interdisciplinary approaches methodologies motivated fundamental questions key high-performing

Язык: Английский

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Gene therapy: Comprehensive overview and therapeutic applications

Life Sciences, Год журнала: 2022, Номер 294, С. 120375 - 120375

Опубликована: Фев. 3, 2022

Язык: Английский

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AAV vectors: The Rubik’s cube of human gene therapy

Molecular Therapy, Год журнала: 2022, Номер 30(12), С. 3515 - 3541

Опубликована: Окт. 6, 2022

Defective genes account for ∼80% of the total more than 7,000 diseases known to date. Gene therapy brings promise a one-time treatment option that will fix errors in patient genetic coding. Recombinant viruses are highly efficient vehicles vivo gene delivery. Adeno-associated virus (AAV) vectors offer unique advantages, such as tissue tropism, specificity transduction, eliciting relatively low immune responses, no incorporation into host chromosome, and long-lasting delivered expression, making them most popular viral delivery system clinical trials, with three AAV-based drugs already approved by US Food Drug Administration (FDA) or European Medicines Agency (EMA). Despite success AAV vectors, their usage particular scenarios is still limited due remaining challenges, poor transduction efficiency certain tissues, organ specificity, pre-existing humoral immunity capsids, vector dose-dependent toxicity patients. In present review, we address different approaches improve focus on capsid selection engineering, strategies overcome anti-AAV response, genome design, ending glimpse at production methods current state recombinant (rAAV) level.

Язык: Английский

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In vivo gene delivery mediated by non-viral vectors for cancer therapy

Journal of Controlled Release, Год журнала: 2020, Номер 325, С. 249 - 275

Опубликована: Июль 4, 2020

Язык: Английский

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Viral vector‐based gene therapies in the clinic

Bioengineering & Translational Medicine, Год журнала: 2021, Номер 7(1)

Опубликована: Сен. 14, 2021

Abstract Gene therapies are currently one of the most investigated therapeutic modalities in both preclinical and clinical settings have shown promise treating a diverse spectrum diseases. aim at introducing gene material target cells represent promising approach to cure diseases that were thought be incurable by conventional modalities. In many cases, therapy requires vector deliver therapeutics into cells; viral vectors among widely studied owing their distinguished advantages such as outstanding transduction efficiency. With decades development, vector‐based achieved outcomes with products approved for range including cancer, infectious monogenic addition, number active trials underway further expand potential. this review, we highlight diversity vectors, review products, discuss current landscape vivo therapies. We reviewed 13 applications. also analyzed more than 200 based on various discussed respective Moreover, provide critical analysis major translational challenges possible strategies address same.

Язык: Английский

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