Delivery of reprogramming factors into fibroblasts for generation of non-genetic induced pluripotent stem cells using a cationic bolaamphiphile as a non-viral vector

Khan, Majad; Narayanan, Karthikeyan; Lu, Hongfang; Choo, Yang; Du, Chan; Wiradharma, Nikken; Yang, Yi-Yan; Wan, Andrew C.A.

doi:10.1016/j.biomaterials.2013.03.072

Cited by 50 publications

(45 citation statements)

References 36 publications

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“…For the delivery of reprogramming factors in nanoparticle form, protein-encapsulated cationic bolaamphiphile sub-micron sized particles were also introduced for generating hiPSCs [41]. Cationic 1,12-aminododecane based bolaamphiphile has a central hydrophobic core for formation of stable structures by hydrophobic interaction between carrier and protein cargo.…”

Section: Non-viral Methods For Reprogramming To Pluripotency and Dmentioning

confidence: 99%

A biomaterial approach to cell reprogramming and differentiation

Long

Kim

et al. 2017

J. Mater. Chem. B

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Cell reprogramming of somatic cells into pluripotent states and subsequent differentiation into certain phenotypes has helped progress regenerative medicine research and other medical applications. Recent research has used viral vectors to induce this reprogramming; however, limitations include low efficiency and safety concerns. In this review, we discuss how biomaterial methods offer potential avenues for either increasing viability and downstream applicability of viral methods, or providing a safer alternative. The use of non-viral delivery systems, such as electroporation, micro/nanoparticles, nucleic acids and the modulation of culture substrate topography and stiffness have generated valuable insights regarding cell reprogramming.

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Section: Non-viral Methods For Reprogramming To Pluripotency and Dmentioning

confidence: 99%

A biomaterial approach to cell reprogramming and differentiation

Long

Kim

et al. 2017

J. Mater. Chem. B

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“…Several non‐viral vectors have been described for iPSC reprogramming which circumvent the problems of viral vectors. These include episomal vectors , minicircle (mc) vectors , synthetic RNA replicons , human artificial chromosomes , transposon systems and nanoparticle carriers .…”

Section: Recent Advances In Pluripotency Reprogrammingmentioning

confidence: 99%

“…For example, using cationic Bolaamphiphile coupled with Klf4, Nanog, NR5A2 (orphan nuclear receptor) and Sox2, Khan et al . successfully reprogrammed human fibroblasts . Using a different cationic lipid carrier, Lipofectamine RNAiMAX (LF), fused with OSKM mRNAs, Tavernier et al .…”

Section: Recent Advances In Pluripotency Reprogrammingmentioning

confidence: 99%

Inducing pluripotency in vitro: recent advances and highlights in induced pluripotent stem cells generation and pluripotency reprogramming

et al. 2015

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Induced pluripotent stem cells (iPSCs) are considered patient-specific counterparts of embryonic stem cells as they originate from somatic cells after forced expression of pluripotency reprogramming factors Oct4, Sox2, Klf4 and c-Myc. iPSCs offer unprecedented opportunity for personalized cell therapies in regenerative medicine. In recent years, iPSC technology has undergone substantial improvement to overcome slow and inefficient reprogramming protocols, and to ensure clinical-grade iPSCs and their functional derivatives. Recent developments in iPSC technology include better reprogramming methods employing novel delivery systems such as non-integrating viral and non-viral vectors, and characterization of alternative reprogramming factors. Concurrently, small chemical molecules (inhibitors of specific signalling or epigenetic regulators) have become crucial to iPSC reprogramming; they have the ability to replace putative reprogramming factors and boost reprogramming processes. Moreover, common dietary supplements, such as vitamin C and antioxidants, when introduced into reprogramming media, have been found to improve genomic and epigenomic profiles of iPSCs. In this article, we review the most recent advances in the iPSC field and potent application of iPSCs, in terms of cell therapy and tissue engineering.

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“…To overcome these shortcomings, a transient non-DNA or non-viral approach is highly desirable. Protein delivery serves as a safe alternative and there are a number of protein delivery technologies, such as fusions to cell penetrating peptide derived from Tat protein of retrovirus [15], [16], however, they are limited by the protein purification and low targeting efficiency.…”

Section: Introductionmentioning

confidence: 99%

Bacterial Delivery of TALEN Proteins for Human Genome Editing

et al. 2014

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Transcription Activator-Like Effector Nucleases (TALENs) are a novel class of sequence-specific nucleases that have recently gained prominence for its ease of production and high efficiency in genome editing. A TALEN pair recognizes specific DNA sequences and introduce double-strand break in the target site, triggering non-homologous end joining and homologous recombination. Current methods of TALEN delivery involves introduction of foreign genetic materials, such as plasmid DNA or mRNA, through transfection. Here, we show an alternative way of TALEN delivery, bacterial type III secretion system (T3SS) mediated direct injection of the TALEN proteins into human cells. Bacterially injected TALEN was shown to efficiently target host cell nucleus where it persists for almost 12 hours. Using a pair of TALENs targeting venus gene, such injected nuclear TALENs were shown functional in introducing DNA mutation in the target site. Interestingly, S-phase cells seem to show greater sensitivity to the TALEN mediated target gene modification. Accordingly, efficiency of such genome editing can easily be manipulated by the infection dose, number of repeated infections as well as enrichment of S phase cells. This work further extends the utility of T3SS in the delivery of functional proteins into mammalian cells to alter their characters for biomedical applications.

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Delivery of reprogramming factors into fibroblasts for generation of non-genetic induced pluripotent stem cells using a cationic bolaamphiphile as a non-viral vector

Cited by 50 publications

References 36 publications

A biomaterial approach to cell reprogramming and differentiation

A biomaterial approach to cell reprogramming and differentiation

Inducing pluripotency in vitro: recent advances and highlights in induced pluripotent stem cells generation and pluripotency reprogramming

Bacterial Delivery of TALEN Proteins for Human Genome Editing

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