Publications by authors named "Bhaargavi Ashok"

2 Publications

  • Page 1 of 1

Lipid- and Polymer-Based Nanoparticle Systems for the Delivery of CRISPR/Cas9.

J Drug Deliv Sci Technol 2021 Oct 11;65. Epub 2021 Jul 11.

Department of Biomedical Engineering and Chemical Engineering, The University of Texas at San Antonio, San Antonio, TX, USA.

The discovery of clustered regularly interspaced short palindromic repeat (CRISPR)/ CRISPR-associated (Cas) genome editing systems and their applications in human health and medicine has heralded a new era of biotechnology. However, the delivery of CRISPR therapeutics is arguably the most difficult barrier to overcome for translation to clinical administration. Appropriate delivery methods are required to efficiently and selectively transport all gene editing components to specific target cells and tissues of interest, while minimizing off-target effects. To overcome this challenge, we discuss and critic nanoparticle delivery strategies, focusing on the use of lipid-based and polymeric-based matrices herein.
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http://dx.doi.org/10.1016/j.jddst.2021.102728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318345PMC
October 2021

CRISPR/Cas systems to overcome challenges in developing the next generation of T cells for cancer therapy.

Adv Drug Deliv Rev 2020 21;158:17-35. Epub 2020 Jul 21.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX 78712, USA; McKetta Department of Chemical Engineering, The University of Texas at Austin, Austin, TX 78712, USA; Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA; Departments of Pediatrics and Surgery, Dell Medical School, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address:

Genetically engineered immune cells with chimeric antigen receptors (CAR) or modified T cell receptors (TCR) have demonstrated their potential as a potent class of new cancer therapeutic strategy. Despite the clinical success of autologous CD19 CAR T cells in hematological malignancies, allogeneic T cells exhibit many advantages over their autologous counterparts and have recently gathered widespread attention due to the emergence of multiplex genome editing techniques, particularly CRISPR/Cas systems. Furthermore, genetically engineered T cells face a host of major challenges in solid tumors that are not as significant for blood cancers such as T cell targeted delivery, target specificity, proliferation, persistence, and the immunosuppressive tumor microenvironment. We take this opportunity to analyze recent strategies to develop allogeneic T cells, specifically in consideration of CRISPR/Cas and its delivery systems for multiplex gene editing. Additionally, we discuss the current methods used to delivery CRISPR/Cas systems for immunotherapeutic applications, and the challenges to continued development of novel delivery systems. We also provide a comprehensive analysis of the major challenges that genetically engineered T cells face in solid tumors along with the most recent strategies to overcome these barriers, with an emphasis on CRISPR-based approaches. We illustrate the synergistic prospects for how the combination of synthetic biology and immune-oncology could pave the way for designing the next generation of precision cancer therapy.
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http://dx.doi.org/10.1016/j.addr.2020.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736063PMC
September 2021
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