Supramolecular nanosubstrate–mediated delivery system enables CRISPR-Cas9 knockin of hemoglobin beta gene for hemoglobinopathies

Yang, Peng; Chou, Shih Jie; Li, Jindian; Hui, Wenqiao; Liu, Wenfei; Sun, Na; Zhang, Ryan Y.; Zhu, Yazhen; Tsai, Ming Long; Lai, Henkie Isahwan Ahmad Mulyadi; Smalley, Matthew; Zhang, Xinyue; Chen, Jiayuan; Romero, Zulema; Liu, Dahai; Ke, Zunfu; Zou, Chang; Lee, Chin Fa; Jonas, Steven J.; Ban, Qian; Weiss, Paul S.; Kohn, Donald B.; Chen, Kai; Chiou, Shih Hwa; Tseng, Hsian‐Rong

doi:10.1126/sciadv.abb7107

Cited by 30 publications

(18 citation statements)

References 43 publications

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“…This implies that inhibition of ASK1 is an effective strategy for the treatment of hepatic IRI. Viral-based methods present an effective choice for the delivery of genes in gene therapies, with adeno-associated virus (AAV) being the most promising viral vector [ 166 ]. However, limitations such as packaging capacity (<4.7 kb), safety concern correlated to immunogenicity, and high cost associated with AAV restrain application of AAVs in gene therapy [ 167 ].…”

Section: Remedies Of Hepatic Irimentioning

confidence: 99%

Targeting the Hepatic Microenvironment to Improve Ischemia/Reperfusion Injury: New Insights into the Immune and Metabolic Compartments

Gao¹,

Qiu²,

Wang³

et al. 2022

Aging and disease

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Hepatic ischemia/reperfusion injury (IRI) is mainly characterized by high activation of immune inflammatory responses and metabolic responses. Understanding the molecular and metabolic mechanisms underlying development of hepatic IRI is critical for developing effective therapies for hepatic IRI. Recent advances in research have improved our understanding of the pathogenesis of IRI. During IRI, hepatocyte injury and inflammatory responses are mediated by crosstalk between the immune cells and metabolic components. This crosstalk can be targeted to treat or reverse hepatic IRI. Thus, a deep understanding of hepatic microenvironment, especially the immune and metabolic responses, can reveal new therapeutic opportunities for hepatic IRI. In this review, we describe important cells in the liver microenvironment (especially non-parenchymal cells) that regulate immune inflammatory responses. The role of metabolic components in the diagnosis and prevention of hepatic IRI are discussed. Furthermore, recent updated therapeutic strategies based on the hepatic microenvironment, including immune cells and metabolic components, are highlighted.

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Section: Remedies Of Hepatic Irimentioning

confidence: 99%

Targeting the Hepatic Microenvironment to Improve Ischemia/Reperfusion Injury: New Insights into the Immune and Metabolic Compartments

Gao¹,

Qiu²,

Wang³

et al. 2022

Aging and disease

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show abstract

“…In one study, SMNPs encapsulating plasmid encoding Cas9 and a guide targeting a safe-harbor locus and, separately, a plasmid encoding GFP plus a functional donor induced the correction of RS1 in vitro following intravitreal injection in a mouse model ( Chou et al, 2020 ). Nanowire-grafted SMNPs were optimized to package and deliver RNPs as well, inducing successful disruption of the dystrophin gene and knock-in of the HBB gene ( Yang et al, 2020 ; Ban et al, 2021 ). Similarly, Wan et al (2020) used disulfide-bridged biguanidyl adamantane (Ad-SS-GD) with CD-PEI as components for supramolecular assembly for the packaging and delivery of Cas9 RNPs and successfully induced nearly 16% editing in SW-280 cells.…”

Section: Particle-based Deliverymentioning

confidence: 99%

Delivering the CRISPR/Cas9 system for engineering gene therapies: Recent cargo and delivery approaches for clinical translation

Foley

Sims

Duggan

et al. 2022

Front. Bioeng. Biotechnol.

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Clustered Regularly Interspaced Short Palindromic Repeats associated protein 9 (CRISPR/Cas9) has transformed our ability to edit the human genome selectively. This technology has quickly become the most standardized and reproducible gene editing tool available. Catalyzing rapid advances in biomedical research and genetic engineering, the CRISPR/Cas9 system offers great potential to provide diagnostic and therapeutic options for the prevention and treatment of currently incurable single-gene and more complex human diseases. However, significant barriers to the clinical application of CRISPR/Cas9 remain. While in vitro, ex vivo, and in vivo gene editing has been demonstrated extensively in a laboratory setting, the translation to clinical studies is currently limited by shortfalls in the precision, scalability, and efficiency of delivering CRISPR/Cas9-associated reagents to their intended therapeutic targets. To overcome these challenges, recent advancements manipulate both the delivery cargo and vehicles used to transport CRISPR/Cas9 reagents. With the choice of cargo informing the delivery vehicle, both must be optimized for precision and efficiency. This review aims to summarize current bioengineering approaches to applying CRISPR/Cas9 gene editing tools towards the development of emerging cellular therapeutics, focusing on its two main engineerable components: the delivery vehicle and the gene editing cargo it carries. The contemporary barriers to biomedical applications are discussed within the context of key considerations to be made in the optimization of CRISPR/Cas9 for widespread clinical translation.

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“…In recent years, gene-editing technology based on the CRISPR/Cas9 system has also been applied in clinical trials of a variety of malignant tumors, showing significant potential ( Table 1 ). The CRISPR/Cas9 system can be introduced in three typical forms: plasmid DNA (pDNA), mRNA, and ribonucleoprotein (RNP, a complex of cas9 protein with sgRNA) ( Yang et al, 2020 ; Duan et al, 2021 ). The pDNA-based CRISPR/Cas9 system generally performed by integrating the both cas9 protein and sgRNA encoding plasmids into a single vector, to avoid multiple transfections.…”

Section: Occurrence and Development Of Gene-editing Technology In Gen...mentioning

confidence: 99%

Research Progress on Gene Editing Based on Nano-Drug Delivery Vectors for Tumor Therapy

Yang

Suo

et al. 2022

Front. Bioeng. Biotechnol.

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Malignant tumors pose a serious threat to human health and have high fatality rates. Conventional clinical anti-tumor treatment is mainly based on traditional surgery, chemotherapy, radiotherapy, and interventional therapy, and even though these treatment methods are constantly updated, a satisfactory efficacy is yet to be obtained. Therefore, research on novel cancer treatments is being actively pursued. We review the classification of gene therapies of malignant tumors and their advantages, as well as the development of gene editing techniques. We further reveal the nano-drug delivery carrier effect in improving the efficiency of gene editing. Finally, we summarize the progress in recent years of gene editing techniques based on nano-drug delivery carriers in the treatment of various malignant tumors, and analyze the prospects of the technique and its restricting factors.

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Supramolecular nanosubstrate–mediated delivery system enables CRISPR-Cas9 knockin of hemoglobin beta gene for hemoglobinopathies

Cited by 30 publications

References 43 publications

Targeting the Hepatic Microenvironment to Improve Ischemia/Reperfusion Injury: New Insights into the Immune and Metabolic Compartments

Targeting the Hepatic Microenvironment to Improve Ischemia/Reperfusion Injury: New Insights into the Immune and Metabolic Compartments

Delivering the CRISPR/Cas9 system for engineering gene therapies: Recent cargo and delivery approaches for clinical translation

Research Progress on Gene Editing Based on Nano-Drug Delivery Vectors for Tumor Therapy

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