Optimization of electroporation and other non‐viral gene delivery strategies for T cells

Harris, Emily; Elmer, Jacob

doi:10.1002/btpr.3066

Cited by 48 publications

(37 citation statements)

References 96 publications

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“…The literature reports an increasing arsenal of non-viral delivery strategies that successfully supply components of the CRISPR/Cas system into the cells (reviewed in [25,118,119]). Several techniques suitable for transfection of other cell types did not prove to be applicable for T cells.…”

Section: Strategies For Delivery Of Crispr/cas Cargo To T Cellsmentioning

confidence: 99%

Challenges of CRISPR-based Gene Editing in Primary T Cells

Rezalotfi¹,

Fritz²,

Förster³

et al. 2022

Preprint

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Adaptive T cell immunotherapy holds great promise for the successful treatment of leukemia as well as other types of cancers. More recently, it was also shown to be an effective treatment option for chronic virus infections in immunosuppressed patients. Autologous or allogeneic T cells used for immunotherapy are usually genetically modified to express novel T cell or chimeric antigen receptors. The production of such cells was significantly simplified with the CRISPR/Cas system allowing deletion or insertion of novel genes at specific locations within the genome. In this review, we describe recent methodological breakthroughs important for the conduction of these genetic modifications, summarize crucial points to be considered when conducting such experiments, and highlight the potential pitfalls of these approaches.

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Section: Strategies For Delivery Of Crispr/cas Cargo To T Cellsmentioning

confidence: 99%

Challenges of CRISPR-based Gene Editing in Primary T Cells

Rezalotfi¹,

Fritz²,

Förster³

et al. 2022

Preprint

View full text Add to dashboard Cite

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“…CARs typically comprise an extracellular binding domain with an antibody's single‐chain variable fragment which targets a tumor biomarker, an intracellular domain for stimulatory signaling, and a transmembrane domain. [ 37 ]…”

Section: Nanotechnology‐mediated Delivery Of Chimeric Antigen Receptorsmentioning

confidence: 99%

“…While effective in achieving stable, long‐term expression of CARs in T cells, viral‐mediated delivery of CAR genes are limited by complex production processes and safety concerns. [ 37,38 ] The large‐scale production of viral vectors is nontrivial, as it requires facilities that adhere to good manufacturing practices. To generate vectors, plasmids encoding the transgene of interest, as well as packaging vectors which encode viral structural components, are introduced into HEK293T cells.…”

Section: Nanotechnology‐mediated Delivery Of Chimeric Antigen Receptorsmentioning

confidence: 99%

Improving the Delivery of Drugs and Nucleic Acids to T Cells Using Nanotechnology

2021

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T cells play several roles in antitumor immunity, including mediating cytotoxicity, generating immune memory, and promoting humoral immunity. Given these critical roles, T cells are the therapeutic target of immunotherapies that have achieved clinical success, notably immune checkpoint inhibitors and chimeric antigen receptor T‐cell therapy. However, a fraction of patients benefits from these treatments due to intolerable toxicities and limited efficacy. These issues stem in part from inefficient and nonselective drug delivery to T cells. Nanotechnology may help resolve these delivery issues, as nanoparticles can serve as modular drug delivery vehicles with targeting abilities that can be applied for ex vivo and in vivo delivery. Herein, applications of nanotechnology in improving extracellular delivery of cytokines and small molecule drugs and intracellular delivery of siRNA to T cells are described. An overview of nanoparticle‐mediated delivery of nucleic acids for chimeric antigen receptor T‐cell therapy and CRISPR/Cas9 genome editing is provided. Finally, an outlook on the challenges and opportunities for the advancement of nanoparticle‐mediated drug delivery to T cells is shared.

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“…However, the complex and expensive manufacturing processes of viral vectors, cumbersome production, quality control steps of viral vector-transfected CAR-T, and inevitable long-term monitoring of unanticipated side effects also limit its wide clinical application. In view of this, non-viral delivery systems with low-cost and high-safety properties have emerged as a better choice [ 108 ].…”

Section: Enhanced Clinical Safety and Accessibility Of Car-t Therapymentioning

confidence: 99%

CAR-T in Cancer Treatment: Develop in Self-Optimization, Win-Win in Cooperation

Guo

Cui

2021

Cancers

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Despite remarkable achievements in the treatment of hematologic malignancies, chimeric antigen receptor (CAR)-T cell therapy still faces many obstacles. The limited antitumor activity and persistence of infused CAR-T cells, especially in solid tumors, are the main limiting factors for CAR-T therapy. Moreover, clinical security and accessibility are important unmet needs for the application of CAR-T therapy. In view of these challenges, many potentially effective solutions have been proposed and confirmed. Both the independent and combined strategies of CAR-T therapy have exhibited good application prospects. Thus, in this review, we have discussed the cutting-edge breakthroughs in CAR-T therapy for cancer treatment, with the aim of providing a reference for addressing the current challenges.

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Optimization of electroporation and other non‐viral gene delivery strategies for T cells

Cited by 48 publications

References 96 publications

Challenges of CRISPR-based Gene Editing in Primary T Cells

Challenges of CRISPR-based Gene Editing in Primary T Cells

Improving the Delivery of Drugs and Nucleic Acids to T Cells Using Nanotechnology

CAR-T in Cancer Treatment: Develop in Self-Optimization, Win-Win in Cooperation

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