Guanidyl-Rich Poly(ß Amino Ester)s for Universal Functional Cytosolic Protein Delivery and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas9 Ribonucleoprotein Based Gene Editing

Article Nanoscience & Nanotechnology

Non-invasive activation of intratumoural gene editing for improved adoptive T-cell therapy in solid tumours

Xiaohong Chen et al.

Summary: The authors develop a temperature-sensitive system for delivering a Cas9 gene-editing sequence to target resistance mechanisms in cancer cells, which enhances T-cell delivery and improves therapeutic outcomes.

NATURE NANOTECHNOLOGY (2023)

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Article Polymer Science

Phosphocholine-Functionalized Zwitterionic Highly Branched Poly(?-amino ester)s for Cytoplasmic Protein Delivery

Yuhe Zhang et al.

Summary: Proteins have great potential in vaccine development and disease treatment, but overcoming biological barriers is necessary for them to exert their specific functions in target tissues. The use of polymers as carriers can improve their bioavailability and efficiency. However, protein packaging and cell membrane penetration without cytotoxicity are challenging due to the presence of both positive and negative charges on protein surfaces. In this study, phosphocholine-functionalized zwitterionic poly(beta-amino ester)s were developed for cytoplasmic protein delivery, showing higher efficiency and lower cytotoxicity compared to other functionalized polymers.

ACS MACRO LETTERS (2023)

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Article Nanoscience & Nanotechnology

Direct Cellular Delivery of Exogenous Genetic Material and Protein via Colloidal Nano-Assemblies with Biopolymer

Ankan Kumar Sarkar et al.

Summary: The direct cytosolic delivery of large biomolecules bypassing endocytic pathways is a promising strategy for therapeutic applications. Recent research has shown that surface chemistry of carriers, nanoscale assembly, colloidal stability, and low surface charge are critical for non-endocytic uptake processes. The guanidinium-terminated polyaspartic acid micelle can deliver protein/DNA directly to the cytosol by forming a nano-assembly with <200 nm size and near-zero surface charge, highlighting the importance of size and colloidal properties for efficient cytosolic delivery of large biomolecules.

ACS APPLIED MATERIALS & INTERFACES (2022)

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Review Pharmacology & Pharmacy

CRISPR/Cas9 ribonucleoprotein-mediated genome and epigenome editing in mammalian cells

Hanan Bloomer et al.

Summary: The CRISPR/Cas system has revolutionized the ability to edit the mammalian genome, providing a platform for correcting pathogenic mutations and studying gene function. Cas9 RNPs, as a delivery method, offer advantages in editing efficiency, off-target editing activity, and cellular toxicity reduction.

ADVANCED DRUG DELIVERY REVIEWS (2022)

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Article Biochemistry & Molecular Biology

Non-viral delivery of CRISPR-Cas9 complexes for targeted gene editing via a polymer delivery system

Jonathan O'Keeffe Ahern et al.

Summary: This study demonstrates the potential of the HPAE-EB polymer for CRISPR-Cas9 genome editing, achieving targeted exon excision in the COL7A1 gene through a dual-RNA guide system. The biophysical properties of HPAE-EB were found to be efficient and cytocompatible in HEK293 cells, with a target genomic excision rate of 15-20%, but showed reduced efficiency in RDEB keratinocytes. However, delivery of CRISPR-Cas9 as a ribonucleoprotein complex increased targeted genomic excision to over 40%.

GENE THERAPY (2022)

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Article Multidisciplinary Sciences

Endowing universal CAR T-cell with immune-evasive properties using TALEN-gene editing

Sumin Jo et al.

Summary: This study describes the development of a novel immune-evasive universal CAR T-cell scaffold, which allows CAR-T cells to evade destruction by host T and NK cells in an allogeneic setting, thereby prolonging their persistence and antitumor activity in vivo.

NATURE COMMUNICATIONS (2022)

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Article Engineering, Biomedical

Reactive oxygen species-responsive branched poly (β-amino ester) with robust efficiency for cytosolic protein delivery

Rujian Lu et al.

Summary: This study developed a ROS-degradable, branched poly(beta-amino ester) (PBAE) for efficient cytosolic protein delivery. The PBAE formed stable nanocomplexes with proteins and could be degraded by H2O2, enabling intracellular protein release. The PBAE achieved high efficiency in delivering proteins of different sizes and isoelectric points into tumor cells.

ACTA BIOMATERIALIA (2022)

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Article Multidisciplinary Sciences

Exosome-mediated delivery of Cas9 ribonucleoprotein complexes for tissue-specific gene therapy of liver diseases

Tao Wan et al.

Summary: CRISPR-Cas9 gene editing is a powerful therapeutic technology, but the lack of safe and efficient in vivo delivery systems limits its clinical applications. Researchers have developed a novel gene editing delivery system, called exosomeRNP, which loads Cas9 RNPs into purified exosomes derived from hepatic stellate cells. exosomeRNP enables effective cytosolic delivery of RNPs in vitro and specifically accumulates in liver tissue in vivo. By targeting different genes, exosomeRNP demonstrates considerable therapeutic potential in acute liver injury, chronic liver fibrosis, and hepatocellular carcinoma mouse models. This study provides a feasible platform for precise and tissue-specific gene therapies for liver diseases.

SCIENCE ADVANCES (2022)

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Article Multidisciplinary Sciences

Genome-editing prodrug: Targeted delivery and conditional stabilization of CRISPR-Cas9 for precision therapy of inflammatory disease

Xiaojie Yan et al.

Summary: The study introduces a CRISPR-Cas9 prodrug nanosystem, NanoProCas9, which demonstrates targeted delivery and conditional activation of CRISPR-Cas9 for precision therapy of inflammatory bowel disease.

SCIENCE ADVANCES (2021)

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Article Cell Biology

Engineered extracellular vesicles as versatile ribonucleoprotein delivery vehicles for efficient and safe CRISPR genome editing

Xingang Yao et al.

Summary: A mechanism to actively enrich RNPs into EVs using RNA aptamer and aptamer-binding protein interactions has been described, resulting in efficient genome editing and transient expression. This system allows for multiplex genome editing targeting multiple loci and can deliver RNPs active in vivo. The data demonstrate that this approach could enhance genome editing efficiency and safety.

JOURNAL OF EXTRACELLULAR VESICLES (2021)

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Review Chemistry, Multidisciplinary

Lipid Nanoparticles-From Liposomes to mRNA Vaccine Delivery, a Landscape of Research Diversity and Advancement

Rumiana Tenchov et al.

Summary: Lipid nanoparticles (LNPs) have become promising vehicles in the pharmaceutical industry for delivering various therapeutics, particularly highlighted in the COVID-19 mRNA vaccines. LNPs exhibit versatility and physical stability, allowing for targeted delivery of therapeutic drugs to specific locations within the body. Liposomes, an early version of LNPs, have already been widely applied in medical practice.

ACS NANO (2021)

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Review Pharmacology & Pharmacy

Highly branched poly(b-amino ester)s for gene delivery in hereditary skin diseases

Ming Zeng et al.

Summary: Non-viral gene therapy using highly branched poly(b-amino ester)s shows promise in treating hereditary skin diseases like recessive dystrophic epidermolysis bullosa (RDEB). The successful restoration of collagen expression with this platform suggests the potential for expedited gene therapy translation for genetic cutaneous disorders.

ADVANCED DRUG DELIVERY REVIEWS (2021)

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Article Chemistry, Multidisciplinary

Rational Design of Poly(disulfide)s as a Universal Platform for Delivery of CRISPR-Cas9 Machineries toward Therapeutic Genome Editing

Jiajing Guo et al.

Summary: Poly(disulfide)s synthesized by ring-opening polymerization demonstrated excellent delivery performance for CRISPR-Cas9-based genome editors, including plasmid, mRNA, and protein. Their ability stems from molecular structures interacting with biomacromolecules, unique delivery pathways mediating cellular uptake, and strong ability to escape the endosome. Degradation by intracellular glutathione promotes timely release of CRISPR-Cas9 machinery and reduces cytotoxicity.

ACS CENTRAL SCIENCE (2021)

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Article Chemistry, Multidisciplinary

Direct Cytosolic Delivery of Proteins through Coengineering of Proteins and Polymeric Delivery Vehicles

Yi-Wei Lee et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2020)

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Article Chemistry, Multidisciplinary

Tailoring guanidyl-rich polymers for efficient cytosolic protein delivery

Jia Lv et al.

JOURNAL OF CONTROLLED RELEASE (2020)

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Article Biotechnology & Applied Microbiology

Lecithin nano-liposomal particle as a CRISPR/Cas9 complex delivery system for treating type 2 diabetes

Eun Yi Cho et al.

JOURNAL OF NANOBIOTECHNOLOGY (2019)

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Article Cell & Tissue Engineering

Highly Efficient and Marker-free Genome Editing of Human Pluripotent Stem Cells by CRISPR-Cas9 RNP and AAV6 Donor-Mediated Homologous Recombination

Renata M. Martin et al.

CELL STEM CELL (2019)

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Article Multidisciplinary Sciences

A boronic acid-rich dendrimer with robust and unprecedented efficiency for cytosolic protein delivery and CRISPR-Cas9 gene editing

Chongyi Liu et al.

SCIENCE ADVANCES (2019)

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Article Nanoscience & Nanotechnology

Gold Nanocluster-Mediated Efficient Delivery of Cas9 Protein through pH-Induced Assembly-Disassembly for Inactivation of Virus Oncogenes

Enguo Ju et al.

ACS APPLIED MATERIALS & INTERFACES (2019)

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Article Multidisciplinary Sciences

An anionic, endosome-escaping polymer to potentiate intracellular delivery of cationic peptides, biomacromolecules, and nanoparticles

Brian C. Evans et al.

NATURE COMMUNICATIONS (2019)

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Article Chemistry, Multidisciplinary

Gal8 Visualization of Endosome Disruption Predicts Carrier-Mediated Biologic Drug Intracellular Bioavailability

Kameron V. Kilchrist et al.

ACS NANO (2019)

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Article Chemistry, Multidisciplinary

Electrostatically Driven Guanidinium Interaction Domains that Control Hydrogel-Mediated Protein Delivery In Vivo

Stephen E. Miller et al.

ACS CENTRAL SCIENCE (2019)

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Article Biochemical Research Methods

A Guanidinium-Rich Polymer for Efficient Cytosolic Delivery of Native Proteins

Chunlei Yu et al.

BIOCONJUGATE CHEMISTRY (2019)

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Review Biochemical Research Methods

Endosomal Escape and Cytosolic Penetration of Macromolecules Mediated by Synthetic Delivery Agents

Dakota J. Brock et al.

BIOCONJUGATE CHEMISTRY (2019)

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Article Multidisciplinary Sciences

Carboxylated branched poly(β-amino ester) nanoparticles enable robust cytosolic protein delivery and CRISPR-Cas9 gene editing

Yuan Rui et al.

SCIENCE ADVANCES (2019)

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Article Pharmacology & Pharmacy

In Vivo Editing of Macrophages through Systemic Delivery of CRISPR-Cas9-Ribonucleoprotein-Nanoparticle Nanoassemblies

Yi-Wei Lee et al.

ADVANCED THERAPEUTICS (2019)

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Article Engineering, Biomedical

Combinatorial library of chalcogen-containing lipidoids for intracellular delivery of genome-editing proteins

Yamin Li et al.

BIOMATERIALS (2018)

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The fluorination effect of fluoroamphiphiles in cytosolic protein delivery

Zhenjing Zhang et al.

NATURE COMMUNICATIONS (2018)

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Fluoropolymers for intracellular and in vivo protein delivery

Jia Lv et al.

BIOMATERIALS (2018)

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Rational Design of a Polymer with Robust Efficacy for Intracellular Protein and Peptide Delivery

Hong Chang et al.

NANO LETTERS (2017)

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Molecular remission of infant B-ALL after infusion of universal TALEN gene-edited CAR T cells

Waseem Qasim et al.

SCIENCE TRANSLATIONAL MEDICINE (2017)

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Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair

Kunwoo Lee et al.

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Cellular uptake of nanoparticles: journey inside the cell

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Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles

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The transition from linear to highly branched poly(β-amino ester)s: Branching matters for gene delivery

Dezhong Zhou et al.

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Fluorinated poly(propylenimine) dendrimers as gene vectors

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Guanidyl-Rich Poly(ß Amino Ester)s for Universal Functional Cytosolic Protein Delivery and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas9 Ribonucleoprotein Based Gene Editing

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