Engineering Efficient CAR-T Cells via Electroactive Nanoinjection

Article Multidisciplinary Sciences

Enhancing CAR-T cell functionality in a patient-specific manner

David K. Y. Zhang et al.

Summary: Personalizing the level of stimulation during T-cell activation enhances CAR-T functionality.

NATURE COMMUNICATIONS (2023)

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Article Materials Science, Multidisciplinary

Efficient non-viral CAR-T cell generation via silicon-nanotube-mediated transfection

Yaping Chen et al.

Summary: Cell-based immunotherapy such as CAR-T therapy shows great potential in treating cancer and other diseases, but its current viral-based method is costly and unsafe. In this study, we demonstrate successful transfection of CAR into primary T cells using SiNT arrays, achieving high efficiency and expression rates. SiNT-interfacing also leads to faster T cell proliferation and enhanced killing ability against lymphoma cells. These findings suggest that a non-viral nanoinjection platform like SiNTs can greatly contribute to the development of effective cell-based therapies.

MATERIALS TODAY (2023)

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Article Nanoscience & Nanotechnology

Spin-Coating-Based Fabrication of Nanostraw Arrays for Cellular Nano-electroporation

Aihua Zhang et al.

Summary: Nano-electroporation technology allows external biomolecules to enter cells using nanostraws. In this study, a simple spin-coating technique was developed to prepare oxide nanostraw arrays, which can be integrated with microfluidic devices for effective cell nano-electroporation. The fabricated nanostraws showed controllable diameters and spacing. They were successfully used for intracellular drug delivery, providing a unique solution for batch fabrication and serving as an essential module for biomedical studies.

ACS APPLIED NANO MATERIALS (2022)

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Article Chemistry, Multidisciplinary

Polymeric Nanoneedle Arrays Mediate Stiffness-Independent Intracellular Delivery

Hao Zhe Yoh et al.

Summary: This study explores cell responses to substrate stiffness by engineering polymeric nanoneedle arrays of different stiffness, demonstrating potential intracellular delivery mechanisms of polymeric nanoneedles through interactions between cells and different polymeric substrates with varying stiffness.

ADVANCED FUNCTIONAL MATERIALS (2022)

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Article Medicine, Research & Experimental

Characterizing piggyBat-a transposase for genetic modification of T cells

Gaurav Sutrave et al.

Summary: CAR T cells targeting CD19 show significant efficacy in treating B cell malignancies, but current manufacturing protocols are complex and costly. This study highlights the potential of utilizing the transposase piggyBat from little brown bats for efficient production of CAR T cells with low variability and similar integration site profiles.

MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT (2022)

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Review Chemistry, Multidisciplinary

Recent Advances in Microscale Electroporation

Sung-Eun Choi et al.

Summary: This article introduces the physical principles and design trends of microscale electroporation devices and discusses their applications in drug development and cell analysis, among other areas.

CHEMICAL REVIEWS (2022)

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Review Nanoscience & Nanotechnology

Biointerface design for vertical nanoprobes

Roey Elnathan et al.

Summary: The design of a vertical nanoprobe biointerface determines its ability to interrogate and control cells, enabling advances in drug delivery, intracellular sampling and sensing, biophysical interaction, and bioelectronics.

NATURE REVIEWS MATERIALS (2022)

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Article Biotechnology & Applied Microbiology

Role of actin cytoskeleton in cargo delivery mediated by vertically aligned silicon nanotubes

Yaping Chen et al.

Summary: Nanofabrication technologies have been used for developing engineered nano-bio interfaces for cellular processes. In this study, the role of actin cytoskeleton in mRNA delivery mediated by silicon nanotubes was investigated. The results suggest that actin inhibition before cell-SiNT interface significantly reduces mRNA delivery, while inhibition after interface establishment has minimal impact. These findings contribute to understanding the mechanisms involved in intracellular delivery and provide insights for designing cell-nano interfaces.

JOURNAL OF NANOBIOTECHNOLOGY (2022)

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Article Chemistry, Multidisciplinary

Use of dielectrophoresis for directing T cells to microwells before nanostraw transfection: modelling and experiments

Mercy Lard et al.

Summary: Nanostraw substrates have the potential to achieve minimally invasive cell transfection, but leakage of current limits the effectiveness of cell coverage. This issue can be addressed by covering the nanostraw substrate with an insulating layer containing pores of similar size to cells.

RSC ADVANCES (2022)

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Review Biochemistry & Molecular Biology

Cell death due to electroporation - A review

Tina Batista Napotnik et al.

Summary: Exposure of cells to high voltage electric pulses can transiently increase membrane permeability through electroporation. Electroporation can be reversible and used in gene transfer and drug delivery, but may also lead to irreversible electroporation causing cell death. Understanding the mechanisms of cell death and membrane repair after electroporation is crucial for optimizing and developing new techniques in medicine, biotechnology, and food technology.

BIOELECTROCHEMISTRY (2021)

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Review Chemistry, Multidisciplinary

A Comprehensive Review on Intracellular Delivery

Dorsa Morshedi Rad et al.

Summary: Intracellular delivery is crucial in various studies, and recent advancements in micro- and nanoengineered platforms have shown great promise in achieving high efficiency and precision. Different approaches, including macro-, micro-, and nanoengineering, play distinct roles in delivering various cargoes into cells with different mechanisms.

ADVANCED MATERIALS (2021)

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Article Chemistry, Multidisciplinary

Nanostraw-Assisted Cellular Injection of Fluorescent Nanodiamonds via Direct Membrane Opening

Elke Hebisch et al.

Summary: Fluorescent nanodiamonds (FND) are promising materials for long term cell labeling and tracking due to their stable fluorescence, biocompatibility, and amenability to functionalization. This study successfully achieved direct delivery of FND to the cytosol using nanostraws and low voltage electroporation pulses, showing efficient and rapid transport of FND into cells. Live cell STED microscopy revealed that cell membranes open entirely on top of nanostraws, supporting the hypothesis that many FND are delivered directly to the cytosol, avoiding endocytosis and lysosomal entrapment.

SMALL (2021)

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Article Chemistry, Multidisciplinary

Nanowire Based Mechanostimulating Platform for Tunable Activation of Natural Killer Cells

Viraj Bhingardive et al.

Summary: The physical characteristics of the nanoenvironment, such as stiffness and nanotopography, have been found to regulate the activity of NK cells, while chemical and mechanical stimuli independently determine the activation of these lymphocytes. This insight into the regulation mechanism of NK cells paves the way for rationally designed nanomaterials for controlled ex vivo activation of NK cells in immunotherapy.

ADVANCED FUNCTIONAL MATERIALS (2021)

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Review Chemistry, Multidisciplinary

Materials for Improving Immune Cell Transfection

Arun R. K. Kumar et al.

Summary: Traditional and emerging materials for immune cell transfection, their strengths and limitations, and commercial development of these tools are discussed. A list of in vitro and in vivo assays, along with relevant protocols, is recommended to enhance the characterization of transfection techniques and uptake by the clinical community. The overall aim is to motivate the development of novel materials to meet rising demand in transfection for clinical CAR-T cell manufacturing.

ADVANCED MATERIALS (2021)

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Article Cell & Tissue Engineering

A novel non-viral delivery method that enables efficient engineering of primary human T cells for ex vivo cell therapy applications

Heather Kavanagh et al.

Summary: The study demonstrates that the Solupore non-viral delivery system can effectively deliver mRNA and CRISPR CAS9 RNP cargos to T cells while maintaining high levels of cell viability. Compared to electroporation, the Solupore system has minimal impact on cell functionality. CAR T cells generated using the Solupore system exhibit efficient cytotoxicity against target cancer cells.

CYTOTHERAPY (2021)

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Review Biochemical Research Methods

Tutorial: using nanoneedles for intracellular delivery

Ciro Chiappini et al.

Summary: The tutorial outlines the development of a nanoinjection workflow, covering selection of nanoneedle devices, cargo loading approaches, strategies for interfacing to biological systems, and bioassays for evaluating intracellular delivery efficacy.

NATURE PROTOCOLS (2021)

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Article Chemistry, Multidisciplinary

Mechanical Stimulation after Centrifuge-Free Nano-Electroporative Transfection Is Efficient and Maintains Long-Term T Cell Functionalities

Andy Tay et al.

Summary: MagNEI is a powerful non-viral transfection technique that achieves high net transfection efficiency in primary human T cells. It utilizes magnetic forces and mechanical stimulation to enhance DNA transfection, promoting membrane repair and preserving key biological attributes for efficient T cell manufacturing.

SMALL (2021)

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Review Virology

Lentiviral Vectors for T Cell Engineering: Clinical Applications, Bioprocessing and Future Perspectives

Roman P. Labbe et al.

Summary: Lentiviral vectors are crucial in the development of T cell therapies such as tisagenlecleucel, axicabtagene ciloleucel, and brexucabtagene autoleucel. However, obstacles remain in making these therapies widely available. The development of GMP-compliant technologies will play a key role in advancing lentiviral vector-engineered T cell therapies.

VIRUSES-BASEL (2021)

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Review Chemistry, Multidisciplinary

Microfluidic and Nanofluidic Intracellular Delivery

Jeongsoo Hur et al.

Summary: This review provides an overview of recent advances in microfluidic and nanofluidic intracellular delivery strategies and discusses new opportunities and challenges for clinical applications. Microfluidic and nanofluidic approaches as emerging solutions have shown remarkable potential for addressing this open challenge.

ADVANCED SCIENCE (2021)

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Review Engineering, Biomedical

Engineering Micro-Nanomaterials for Biomedical Translation

Yaping Chen et al.

Summary: Different types of engineered nano-bio interfaces, driven by various micro/nanoneedles, nanoparticles, organ-on-chip devices, and nanosubstrates, are advancing scientific and technological progress in biomedical research.

ADVANCED NANOBIOMED RESEARCH (2021)

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Article Chemistry, Multidisciplinary

The Good and the Bad of Cell Membrane Electroporation

Katja Balantic et al.

Summary: Electroporation increases cell membrane permeability through high-voltage electric pulses and is widely used in medicine. It helps the entry or exit of hydrophilic molecules but also poses challenges in research and application.

ACTA CHIMICA SLOVENICA (2021)

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Article Pharmacology & Pharmacy

Vertically Aligned Nanostructured Topographies for Human Neural Stem Cell Differentiation and Neuronal Cell Interrogation

Esther Lestrell et al.

Summary: Neurodegenerative disorders are a significant global health concern with limited treatment options. Advances in stem cell therapies, tissue engineering, and nanobiotechnologies offer hope for better therapeutic delivery and tissue repair. Engineered nanomaterials provide specialized microenvironments for studying human neural cells.

ADVANCED THERAPEUTICS (2021)

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Review Biochemistry & Molecular Biology

Viral vector platforms within the gene therapy landscape

Jote T. Bulcha et al.

Summary: The field of gene therapy has made significant progress in combating human diseases and providing hope to patients and families with limited treatment options, but it has also faced setbacks. Viral-based vectors have played a crucial role in developing powerful drug platforms, but challenges still limit their full potential.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Article Materials Science, Multidisciplinary

Engineered nano-bio interfaces for intracellular delivery and sampling: Applications, agency and artefacts

Esther Lestrell et al.

MATERIALS TODAY (2020)

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Review Chemistry, Multidisciplinary

Engineering Biomaterials with Micro/Nanotechnologies for Cell Reprogramming

Jun Fang et al.

ACS NANO (2020)

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Review Chemistry, Multidisciplinary

Nanoneedle Platforms: The Many Ways to Pierce the Cell Membrane

Gen He et al.

ADVANCED FUNCTIONAL MATERIALS (2020)

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Review Chemistry, Multidisciplinary

High-Aspect-Ratio Nanostructured Surfaces as Biological Metamaterials

Stuart G. Higgins et al.

ADVANCED MATERIALS (2020)

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Article Chemistry, Multidisciplinary

Silicon-Nanotube-Mediated Intracellular Delivery Enables Ex Vivo Gene Editing

Yaping Chen et al.

ADVANCED MATERIALS (2020)

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Article Oncology

Pre-clinical assessment of chimeric antigen receptor t cell therapy targeting CD19+B cell malignancy

Sheng- Hu et al.

ANNALS OF TRANSLATIONAL MEDICINE (2020)

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Article Chemistry, Multidisciplinary

The Benefits of Going Small: Nanostructures for Mammalian Cell Transfection

Andy Tay

ACS NANO (2020)

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Review Oncology

Engineering CAR-T Cells for Next-Generation Cancer Therapy

Mihe Hong et al.

CANCER CELL (2020)

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Article Chemistry, Multidisciplinary

Emerging Roles of 1D Vertical Nanostructures in Orchestrating Immune Cell Functions

Yaping Chen et al.

ADVANCED MATERIALS (2020)

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Article Multidisciplinary Sciences

Efficient and nontoxic biomolecule delivery to primary human hematopoietic stem cells using nanostraws

Ludwig Schmiderer et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Review Chemistry, Multidisciplinary

Vertically configured nanostructure-mediated electroporation: a promising route for intracellular regulations and interrogations

Ali-Reza Shokouhi et al.

MATERIALS HORIZONS (2020)

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Review Biochemistry & Molecular Biology

Killing Mechanisms of Chimeric Antigen Receptor (CAR) T Cells

Mohamed-Reda Benmebarek et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

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Article Chemistry, Multidisciplinary

On-Demand Intracellular Delivery of Single Particles in Single Cells by 3D Hollow Nanoelectrodes

Jian-An Huang et al.

NANO LETTERS (2019)

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Review Chemistry, Multidisciplinary

Nanostructured Materials for Intracellular Cargo Delivery

Andy Tay et al.

ACCOUNTS OF CHEMICAL RESEARCH (2019)

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Article Chemistry, Multidisciplinary

Multifunctional Branched Nanostraw-Electroporation Platform for Intracellular Regulation and Monitoring of Circulating Tumor Cells

Gen He et al.

NANO LETTERS (2019)

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Article Nanoscience & Nanotechnology

Intracellular Delivery and Sensing System Based on Electroplated Conductive Nanostraw Arrays

Rui Wen et al.

ACS APPLIED MATERIALS & INTERFACES (2019)

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Article Chemistry, Multidisciplinary

Cellular Deformations Induced by Conical Silicon Nanowire Arrays Facilitate Gene Delivery

Yaping Chen et al.

SMALL (2019)

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Article Chemistry, Multidisciplinary

Self-Powered Intracellular Drug Delivery by a Biomechanical Energy-Driven Triboelectric Nanogenerator

Zhirong Liu et al.

ADVANCED MATERIALS (2019)

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Review Hematology

An introduction to chimeric antigen receptor (CAR) T-cell immunotherapy for human cancer

Steven Feins et al.

AMERICAN JOURNAL OF HEMATOLOGY (2019)

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Article Pharmacology & Pharmacy

Transfection with Nanostructure Electro-Injection is Minimally Perturbative

Andy Tay et al.

ADVANCED THERAPEUTICS (2019)

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Article Chemistry, Multidisciplinary

Fabrication of Various Structures of Nanostraw Arrays and Their Applications in Gene Delivery

Gen He et al.

ADVANCED MATERIALS INTERFACES (2018)

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Review Chemistry, Multidisciplinary

Intracellular Delivery by Membrane Disruption: Mechanisms, Strategies, and Concepts

Martin P. Stewart et al.

CHEMICAL REVIEWS (2018)

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Article Multidisciplinary Sciences

Cell engineering with microfluidic squeezing preserves functionality of primary immune cells in vivo

Tia DiTommaso et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

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Article Multidisciplinary Sciences

Universal intracellular biomolecule delivery with precise dosage control

Y. Cao et al.

SCIENCE ADVANCES (2018)

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Article Nanoscience & Nanotechnology

Nanoscale manipulation of membrane curvature for probing endocytosis in live cells

Wenting Zhao et al.

NATURE NANOTECHNOLOGY (2017)

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Article Engineering, Electrical & Electronic

Electric field enhanced 3D scalable low-voltage nano-spike electroporation system

Kashif Riaz et al.

SENSORS AND ACTUATORS A-PHYSICAL (2017)

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Article Multidisciplinary Sciences

Soft electroporation for delivering molecules into tightly adherent mammalian cells through 3D hollow nanoelectrodes

Valeria Caprettini et al.

SCIENTIFIC REPORTS (2017)

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Review Biochemistry & Molecular Biology

Progress and challenges in viral vector manufacturing

Johannes C. M. van der Loo et al.

HUMAN MOLECULAR GENETICS (2016)

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Review Biochemical Research Methods

Micro-/nanoscale electroporation

Lingqian Chang et al.

LAB ON A CHIP (2016)

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Review Multidisciplinary Sciences

In vitro and ex vivo strategies for intracellular delivery

Martin P. Stewart et al.

NATURE (2016)

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Article Chemistry, Multidisciplinary

Biodegradable Nanoneedles for Localized Delivery of Nanoparticles in Vivo: Exploring the Biointerface

Ciro Chiappini et al.

ACS NANO (2015)

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Article Multidisciplinary Sciences

Iridium oxide nanotube electrodes for sensitive and prolonged intracellular measurement of action potentials

Ziliang Carter Lin et al.

NATURE COMMUNICATIONS (2014)

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Article Chemistry, Multidisciplinary

Nanostraw-Electroporation System for Highly Efficient Intracellular Delivery and Transfection

Xi Xie et al.

ACS NANO (2013)

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Review Oncology

Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors

James N. Kochenderfer et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2013)

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Review Immunology

Adoptive immunotherapy for cancer: harnessing the T cell response

Nicholas P. Restifo et al.

NATURE REVIEWS IMMUNOLOGY (2012)

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Article Biochemical Research Methods

Mammalian cell transfection: the present and the future

Tae Kyung Kim et al.

ANALYTICAL AND BIOANALYTICAL CHEMISTRY (2010)

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Article Multidisciplinary Sciences

Vertical silicon nanowires as a universal platform for delivering biomolecules into living cells

Alex K. Shalek et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2010)

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Article Biochemical Research Methods

Parallel single-cell light-induced electroporation and dielectrophoretic manipulation

Justin K. Valley et al.

LAB ON A CHIP (2009)

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Review Genetics & Heredity

Progress and problems with the use of viral vectors for gene therapy

CE Thomas et al.

NATURE REVIEWS GENETICS (2003)

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Article Biochemistry & Molecular Biology

High-level transgene expression in primary human T lymphocytes and adult bone marrow CD34+ cells via electroporation-mediated gene delivery

VFI Van Tendeloo et al.

GENE THERAPY (2000)

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Engineering Efficient CAR-T Cells via Electroactive Nanoinjection

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