Publications by authors named "Muhammad Ramli"

15 Publications

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A preliminary studies to assess public knowledge of beach safety in east coast Malaysia.

Nat Hazards (Dordr) 2021 Feb 13:1-15. Epub 2021 Feb 13.

Department of Community Medicine, Kuliyyah of Medicine, International Islamic University Malaysia, 25200 Kuantan, Pahang Malaysia.

Rip currents are one of the coastal hazards that put Malaysian beachgoers in a risky position. Most of the drowning accidents that occur at beaches worldwide are closely associated with this phenomenon. Research on rip currents is needed to build an effective measuring tool to overcome these issues. However, to date, research on rip currents is mainly focused on its physical aspects, commonly concentrating on the processes that influence and relate to the rips' generation. As an effort to minimize the negative consequences exerted by the rips, there is an urgent need to enhance the rip-related research in the social sciences field. Comprehensive research that includes all fields might produce more beneficial and reliable information. Therefore, this study intends to examine the level of public understanding of rip currents and beach safety knowledge of the Teluk Cempedak Beach. A questionnaire comprising 5 sections and 31 questions was developed as the primary tool in this study. A total of 60 beachgoers have been surveyed for this preliminary study through a questionnaire to investigate their demographic profile, frequency of visiting the beach, swimming ability, and their knowledge of rip currents and beach safety. The results show that the beachgoers have poor knowledge of rip currents. Conversely, they are observed to have higher beach safety knowledge. Also, the findings help in filling the research gaps of this study in terms of the instrument used for the data collection procedure. Above all, an extension of this study may contribute to the development of beneficial tools in assessing public knowledge on beach safety and rip currents throughout Malaysian beaches.

Supplementary Information: The online version contains supplementary material available at (10.1007/s11069-021-04613-z).
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http://dx.doi.org/10.1007/s11069-021-04613-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882049PMC
February 2021

Effect of Ni on the Suppression of Sn Whisker Formation in Sn-0.7Cu Solder Joint.

Materials (Basel) 2021 Feb 5;14(4). Epub 2021 Feb 5.

Synchrotron Light Research Institute (SLRI), 111 University Avenue, Muang District, Nakhon Ratchasima 30000, Thailand.

The evolution of internal compressive stress from the intermetallic compound (IMC) CuSn growth is commonly acknowledged as the key inducement initiating the nucleation and growth of tin (Sn) whisker. This study investigates the effect of Sn-0.7Cu-0.05Ni on the nucleation and growth of Sn whisker under continuous mechanical stress induced. The Sn-0.7Cu-0.05Ni solder joint has a noticeable effect of suppression by diminishing the susceptibility of nucleation and growth of Sn whisker. By using a synchrotron micro X-ray fluorescence (µ-XRF) spectroscopy, it was found that a small amount of Ni alters the microstructure of CuSn to form a (Cu,Ni)Sn intermetallic layer. The morphology structure of the (Cu,Ni)Sn interfacial intermetallic layer and Sn whisker growth were investigated by scanning electron microscope (SEM) in secondary and backscattered electron imaging mode, which showed that there is a strong correlation between the formation of Sn whisker and the composition of solder alloy. The thickness of the (Cu,Ni)Sn IMC interfacial layer was relatively thinner and more refined, with a continuous fine scallop-shaped IMC interfacial layer, and consequently enhanced a greater incubation period for the nucleation and growth of the Sn whisker. These verification outcomes proposes a scientifically foundation to mitigate Sn whisker growth in lead-free solder joint.
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http://dx.doi.org/10.3390/ma14040738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914571PMC
February 2021

Optimum Extraction Condition of Flower on Antioxidant Activities, Total Phenolic, Total Flavonoid and Total Anthocyanin Contents.

Trop Life Sci Res 2020 Jul 6;31(2):1-17. Epub 2020 Aug 6.

Food Technology Division, School of Industrial Technology, Universiti Sains Malaysia, 11800 USM Pulau Pinang, Malaysia.

is a herbaceous plant with many health benefits. Extraction is crucial to obtain its bioactive components which contribute to its antioxidant properties. Therefore, this study was conducted to find an optimum extraction condition of flower on total phenolic content (TPC) and antioxidant activity (2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging activity) as well as to determine its total flavonoid content (TFC) and anthocyanin content based on the optimum extraction condition generated by Response Surface Methodology (RSM)-Design Expert 7.1.5. TPC, TFC and total anthocyanin of were conducted by Folin Ciocalteu (FC), calorimetric assay and pH differential method, respectively. The ranges of selected independent variables were ethanol concentration (30°C-90% v/v), time (60-120 min) and temperature (30°C-70°C). The optimum extraction condition was obtained at 39.62% v/v ethanol concentration, 90 min and 44.24°C. However, these values were slightly adjusted according to the convenience of equipment to operate in which ethanol concentration was adjusted to 37% v/v, time remain at 90 min and temperature at 45°C. The predicted values of TPC and DPPH radical scavenging activity were 41.60 mg GAE/g dry samples and 68.12% inhibition and were experimentally verified to be 41.17 ± 0.5 mg GAE/g dry samples and 63.53 ± 0.95% inhibition of TPC and DPPH radical scavenging activity respectively. This result has showed RSM can optimise TPC and radical scavenging activity of . Upon the optimum condition, the TFC determined was 187.05 ± 3.18 mg quercetin/g dried sample which was higher than TPC and the total anthocyanin content was 28.60 ± 0.04 mg/L. Hence, the extractable phenolic, flavonoid and anthocyanin compounds indicated that is a good source of natural antioxidant.
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http://dx.doi.org/10.21315/tlsr2020.31.2.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470475PMC
July 2020

Human Pluripotent Stem Cell-Derived Organoids as Models of Liver Disease.

Gastroenterology 2020 10 15;159(4):1471-1486.e12. Epub 2020 Jun 15.

Stem Cell and Regenerative Biology, Genome Institute of Singapore, Singapore. Electronic address:

Background & Aims: There are few in vitro models for studying the 3-dimensional interactions among different liver cell types during organogenesis or disease development. We aimed to generate hepatic organoids that comprise different parenchymal liver cell types and have structural features of the liver, using human pluripotent stem cells.

Methods: We cultured H1 human embryonic stem cells (WA-01, passage 27-40) and induced pluripotent stem cells (GM23338) with a series of chemically defined and serum-free media to induce formation of posterior foregut cells, which were differentiated in 3 dimensions into hepatic endoderm spheroids and stepwise into hepatoblast spheroids. Hepatoblast spheroids were reseeded in a high-throughput format and induced to form hepatic organoids; development of functional bile canaliculi was imaged live. Levels of albumin and apolipoprotein B were measured in cell culture supernatants using an enzyme-linked immunosorbent assay. Levels of gamma glutamyl transferase and alkaline phosphatase were measured in cholangiocytes. Organoids were incubated with troglitazone for varying periods and bile transport and accumulation were visualized by live-imaging microscopy. Organoids were incubated with oleic and palmitic acid, and formation of lipid droplets was visualized by staining. We compared gene expression profiles of organoids incubated with free fatty acids or without. We also compared gene expression profiles between liver tissue samples from patients with nonalcoholic steatohepatitis (NASH) versus without. We quantified hepatocyte and cholangiocyte populations in organoids using immunostaining and flow cytometry; cholangiocyte proliferation of cholangiocytes was measured. We compared the bile canaliculi network in the organoids incubated with versus without free fatty acids by live imaging.

Results: Cells in organoids differentiated into hepatocytes and cholangiocytes, based on the expression of albumin and cytokeratin 7. Hepatocytes were functional, based on secretion of albumin and apolipoprotein B and cytochrome P450 activity; cholangiocytes were functional, based on gamma glutamyl transferase and alkaline phosphatase activity and proliferative responses to secretin. The organoids organized a functional bile canaliculi system, which was disrupted by cholestasis-inducing drugs such as troglitazone. Organoids incubated with free fatty acids had gene expression signatures similar to those of liver tissues from patients with NASH. Incubation of organoids with free fatty acid-enriched media resulted in structural changes associated with nonalcoholic fatty liver disease, such as decay of bile canaliculi network and ductular reactions.

Conclusions: We developed a hepatic organoid platform with human cells that can be used to model complex liver diseases, including NASH.
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http://dx.doi.org/10.1053/j.gastro.2020.06.010DOI Listing
October 2020

Self-assembled reduced graphene oxide nanoflakes assisted by post-sonication boosted electrical performance in gold interdigitated microelectrodes.

J Colloid Interface Sci 2020 Oct 23;577:345-354. Epub 2020 May 23.

School of Microelectronic Engineering, Universiti Malaysia Perlis, Pauh Putra Campus, 02600 Arau, Perlis, Malaysia.

Reduced graphene oxide (rGO) is widely utilised to develop various types of biosensors; however, producing self-assembled rGO nanoflake networks through single-droplet drop-casting remains inconsistent. In the present work, we systematically used three different methods to prepare rGO suspensions in order to produce large scale self-assembled rGO nanoflake networks through single-droplet drop-casting. The rGO suspensions were prepared using only deionised water with no added any chemicals/organic solvents, which we considered to be a low-cost method. Subsequently, the most effective preparation method was used to deposit rGO nanoflakes onto commercial gold interdigitated microelectrodes (Au-IDE) to examine their electrical performance. Assessment of the yields, developed methods, surface morphologies, spectroscopy and structural analyses of the as-prepared rGO nanoflakes were conducted. The results revealed that method-3 (involving sonication, centrifugation and post-sonication) produced large self-assembled rGO nanoflake networks with strong adhesion to glass substrates. Furthermore, the as-prepared rGO/Au-IDE modified sensors showed excellent electron mobility where the electrical conductivity was enhanced approximately ~ 1000 fold compared to the bare devices. The present work provided new insights for depositing large self-assembled interconnected rGO nanoflake networks through single-droplet drop-casting which will be beneficial for biosensor development and other downstream applications.
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http://dx.doi.org/10.1016/j.jcis.2020.05.070DOI Listing
October 2020

A Chemically Defined Feeder-free System for the Establishment and Maintenance of the Human Naive Pluripotent State.

Stem Cell Reports 2019 10 12;13(4):612-626. Epub 2019 Sep 12.

Stem Cell and Regenerative Biology, Genome Institute of Singapore, 60 Biopolis Street, Singapore 138672, Singapore. Electronic address:

The distinct states of pluripotency in the pre- and post-implantation embryo can be captured in vitro as naive and primed pluripotent stem cell cultures, respectively. The study and application of the naive state remains hampered, particularly in humans, partially due to current culture protocols relying on extraneous undefined factors such as feeders. Here we performed a small-molecule screen to identify compounds that facilitate chemically defined establishment and maintenance of human feeder-independent naive embryonic (FINE) stem cells. The expression profile in genic and repetitive elements of FINE cells resembles the 8-cell-to-morula stage in vivo, and only differs from feeder-dependent naive cells in genes involved in cell-cell/cell-matrix interactions. FINE cells offer several technical advantages, such as increased amenability to transfection and a longer period of genomic stability, compared with feeder-dependent cells. Thus, FINE cells will serve as an accessible and useful system for scientific and translational applications of naïve pluripotent stem cells.
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http://dx.doi.org/10.1016/j.stemcr.2019.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829768PMC
October 2019

Monitoring Breathing Muscle Performance During Singing Noninvasively Using Mechanomyography and Electromyography.

J Voice 2020 Nov 9;34(6):862-869. Epub 2019 Jul 9.

Department of Rehabilitation Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

Objectives: The aim of this study was to investigate the performance of mechanomyography (MMG) and electromyography (EMG) in monitoring the sternocleidomastoid (SCM) as accessory respiratory muscles when breathing during singing.

Methods: MMG and EMG were used to record the activity of the SCM in 32 untrained singers reciting a monotonous text and a standard folk song. Their voices were recorded and their pitch, or fundamental frequency (FF), and intensity were derived using Praat software. Instants of inhale and exhales were identified during singing from their voice recordings and the corresponding SCM MMG and EMG activities were analysed.

Results: The SCM MMG, and EMG signals during breathing while singing were significantly different than breathing at rest (p < 0.001). On the other hand, MMG was relatively better correlated to voice intensity in both reading and singing than EMG. EMG was better, but not significantly, correlated with FF in both reading and singing as compared to MMG.

Conclusions: This study established MMG and EMG as the quantitative measurement tool to monitor breathing activities during singing. This is useful for applications related to singing therapy performance measure including potentially pathologically effected population. While the MMG and EMG could not distinguish FF and intensity significantly, it is useful to serve as a proxy of inhalation and exhalation levels throughout a particular singing session. Further studies are required to determine its efficacy in a therapeutic setting.
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http://dx.doi.org/10.1016/j.jvoice.2019.06.006DOI Listing
November 2020

Reliability and Validity of the Contingent Valuation Method for Estimating Willingness to Pay: A Case of In Vitro Fertilisation.

Appl Health Econ Health Policy 2019 02;17(1):103-110

National Perinatal Epidemiology and Statistics Unit, Centre for Big Data Research in Health and School of Women's and Children's Health, University of New South Wales, Sydney, Australia.

Background: The contingent valuation (CV) method is an alternative approach to typical health economic methods for valuing interventions that have both health and non-health outcomes. Fertility treatment, such as in vitro fertilisation (IVF), fall into this category because of the significant non-health outcomes associated with having children.

Aim: To estimate the general population's willingness to pay (WTP) for one cycle of IVF and one year of IVF treatment, and to test the reliability and validity of a CV instrument.

Methods: Three online CV surveys were administered to a total of 1870 participants from the Australian general population using an ex-post perspective, that is, they assumed they were infertile and needed IVF to conceive a child. Participants answered questions with starting point WTP bids of 2018 Australian dollars (AU$) 4000 or $10,000 for the cost of one IVF cycle, and treatment success rates of 10%, 20% and 50% per IVF cycle. Tests for reliability, internal construct validity, starting point bias, and external validity were performed.

Results: Depending on the success rate and the starting point WTP bid, the mean WTP for one IVF cycle ranged from $6135 to $13,561, while the mean WTP for one year of IVF treatment varied from $17,080 to $31,006. The CV method was reliable and satisfied internal construct and external criterion validity. However strong starting point bias was evident, rendering the mean WTP values highly imprecise.

Conclusion: The CV method holds promise for eliciting the value of interventions, such as fertility treatment, that have significant health and non-health outcomes. Survey instruments that prevent starting point bias are essential. Comparing the results of CV methods to other value elicitation methods is needed to confirm convergent validity.
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http://dx.doi.org/10.1007/s40258-018-0433-3DOI Listing
February 2019

Systemic lidocaine inhibits high-mobility group box 1 messenger ribonucleic acid expression and protein in BALB/c mice after closed fracture musculoskeletal injury.

Saudi J Anaesth 2018 Jul-Sep;12(3):395-398

Department of Anesthesiology, Faculty of Medicine, Hasanuddin University, Makassar, Indonesia.

Background: Severe musculoskeletal trauma can trigger an inflammatory response, and an excessive inflammatory response can lead to systemic inflammatory response syndrome and multiorgan failure. High-mobility group box 1 (HMGB1) is an early mediator pro-inflammatory cytokine in sterile injuries and a late cytokine mediator in infection and sepsis. Previous research has shown that administration of systemic lidocaine can inhibit HMGB1 expression in macrophages of septic rats. The aim of this study was to demonstrate the efficacy of systemic lidocaine to inhibit HMGB1 mRNA and protein in a BALB/c mouse model of sterile inflammation due to closed fracture musculoskeletal injury.

Materials And Methods: Twenty adult male BALB/c mice were divided into lidocaine and control groups. The closed fracture musculoskeletal injury was performed by breaking the left thigh bone of the mice. Four hours after undergoing the closed fracture, the lidocaine group was treated with lidocaine intravenous (2 mg/kg). The same volume of distilled water was injected into the control group instead of lidocaine. HMGB1 mRNA expression was examined with real-time polymerase chain reaction, and HMGB1 protein level was determined with enzyme-linked immunosorbent assay.

Results: The expression of HMGB1 mRNA and protein levels in mice that sustained inflammation due to a closed fracture musculoskeletal injury was significantly decreased in the lidocaine group ( < 0.00 and < 0.00 for mRNA and protein, respectively).

Conclusions: Intravenous administration of lidocaine effectively inhibited the inflammatory process in BALB/c mice that underwent closed fracture musculoskeletal injury by suppressing HMGB1 mRNA transcription and HMGB1 protein translation.
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http://dx.doi.org/10.4103/sja.SJA_685_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6044174PMC
August 2018

An impedimetric micro-immunosensing assay to detect Alzheimer's disease biomarker: Aβ40.

Anal Biochem 2018 08 4;555:12-21. Epub 2018 Jun 4.

Electrochemical Material and Sensors (EmaS) Group, Faculty of Applied Sciences, Universiti Teknologi MARA, 40450 Shah Alam, Selangor, Malaysia; Faculty of Applied Sciences, Universiti Teknologi MARA, Tapah Campus, 35400 Tapah Road, Perak, Malaysia. Electronic address:

A miniaturized biosensing platform, based on monoclonal amyloid-beta antibodies (mAβ) that were immobilized on a disc-shaped platinum/iridium (Pt/Ir) microelectrode surface coupled with an impedimetric signal transducer, was developed for the label-free and sensitive detection of amyloid-beta peptide fragment 1-40 (Aβ40); a reliable biomarker for early diagnosis of Alzheimer's disease (AD). A Pt/Ir microelectrode was electropolymerized with poly (ortho-phenylenediamine), a conducting free amine-containing aromatic polymer; followed by crosslinking with glutaraldehyde for subsequent coupling of mAβ on the microelectrode surface. This modification strategy efficiently improved the impedimetric detection performance of Aβ40 in terms of charge transfer resistance (∼400-fold difference) and normalized impedance magnitude percentage change (∼40% increase) compared with a passive adsorption-based immobilization method. The sensitivity of the micro-immunosensing assay was found to be 1056 kΩ/(pg/mL)/cm and the limit of detection was found to be 4.81 pg/mL with a dynamic range of 1-10 pg/mL (R = 0.9932). The overall precision of the assay, as measured by relative standard deviation, ranged from 0.84 to 5.15%, demonstrating its reliability and accuracy; while in respect to assay durability and stability, the immobilized mAβ were able to maintain 80% of their binding activity to Aβ40 after incubation for 48 h at ambient temperature (25 °C). To validate the practical applicability, the assay was tested using brain tissue lysates prepared from AD-induced rats. Results indicate that the proposed impedimetric micro-immunosensing platform is highly versatile and adaptable for the quantitative detection of other disease-related biomarkers.
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http://dx.doi.org/10.1016/j.ab.2018.05.031DOI Listing
August 2018

Rapid Control of Genome Editing in Human Cells by Chemical-Inducible CRISPR-Cas Systems.

Methods Mol Biol 2018 ;1772:267-288

School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, Singapore.

Genome editing using programmable DNA endonucleases enables the engineering of eukaryotic cells and living organisms with desirable properties or traits. Among the various molecular scissors that have been developed to date, the most versatile and easy-to-use family of nucleases derives from CRISPR-Cas, which exists naturally as an adaptive immune system in bacteria. Recent advances in the CRISPR-Cas technology have expanded our ability to manipulate complex genomes for myriad biomedical and biotechnological applications. Some of these applications are time-sensitive or demand high spatial precision. Here, we describe the use of an inducible CRISPR-Cas9 system, termed iCas, which we have developed to enable rapid and tight control of genome editing in mammalian cells. The iCas system can be switched on or off as desired through the introduction or removal of the small molecule tamoxifen or its related analogs such as 4-hydroxytamoxifen (4-HT).
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http://dx.doi.org/10.1007/978-1-4939-7795-6_15DOI Listing
February 2019

A reassessment of the early archaeological record at Leang Burung 2, a Late Pleistocene rock-shelter site on the Indonesian island of Sulawesi.

PLoS One 2018 11;13(4):e0193025. Epub 2018 Apr 11.

Centre for Archaeological Science, School of Earth & Environmental Sciences, University of Wollongong, Wollongong, New South Wales, Australia.

This paper presents a reassessment of the archaeological record at Leang Burung 2, a key early human occupation site in the Late Pleistocene of Southeast Asia. Excavated originally by Ian Glover in 1975, this limestone rock-shelter in the Maros karsts of Sulawesi, Indonesia, has long held significance in our understanding of early human dispersals into 'Wallacea', the vast zone of oceanic islands between continental Asia and Australia. We present new stratigraphic information and dating evidence from Leang Burung 2 collected during the course of our excavations at this site in 2007 and 2011-13. Our findings suggest that the classic Late Pleistocene modern human occupation sequence identified previously at Leang Burung 2, and proposed to span around 31,000 to 19,000 conventional 14C years BP (~35-24 ka cal BP), may actually represent an amalgam of reworked archaeological materials. Sources for cultural materials of mixed ages comprise breccias from the rear wall of the rock-shelter-remnants of older, eroded deposits dated to 35-23 ka cal BP-and cultural remains of early Holocene antiquity. Below the upper levels affected by the mass loss of Late Pleistocene deposits, our deep-trench excavations uncovered evidence for an earlier hominin presence at the site. These findings include fossils of now-extinct proboscideans and other 'megafauna' in stratified context, as well as a cobble-based stone artifact technology comparable to that produced by late Middle Pleistocene hominins elsewhere on Sulawesi.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193025PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5894965PMC
July 2018

Early human symbolic behavior in the Late Pleistocene of Wallacea.

Proc Natl Acad Sci U S A 2017 04 3;114(16):4105-4110. Epub 2017 Apr 3.

Australian Research Centre for Human Evolution, Environmental Futures Research Institute, Griffith University, Brisbane, QLD, Australia 4111.

Wallacea, the zone of oceanic islands separating the continental regions of Southeast Asia and Australia, has yielded sparse evidence for the symbolic culture of early modern humans. Here we report evidence for symbolic activity 30,000-22,000 y ago at Leang Bulu Bettue, a cave and rock-shelter site on the Wallacean island of Sulawesi. We describe hitherto undocumented practices of personal ornamentation and portable art, alongside evidence for pigment processing and use in deposits that are the same age as dated rock art in the surrounding karst region. Previously, assemblages of multiple and diverse types of Pleistocene "symbolic" artifacts were entirely unknown from this region. The Leang Bulu Bettue assemblage provides insight into the complexity and diversification of modern human culture during a key period in the global dispersal of our species. It also shows that early inhabitants of Sulawesi fashioned ornaments from body parts of endemic animals, suggesting modern humans integrated exotic faunas and other novel resources into their symbolic world as they colonized the biogeographically unique regions southeast of continental Eurasia.
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http://dx.doi.org/10.1073/pnas.1619013114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5402422PMC
April 2017

A chemical-inducible CRISPR-Cas9 system for rapid control of genome editing.

Nat Chem Biol 2016 Nov 12;12(11):980-987. Epub 2016 Sep 12.

Genome Institute of Singapore, Agency for Science Technology and Research, Singapore.

CRISPR-Cas9 has emerged as a powerful technology that enables ready modification of the mammalian genome. The ability to modulate Cas9 activity can reduce off-target cleavage and facilitate precise genome engineering. Here we report the development of a Cas9 variant whose activity can be switched on and off in human cells with 4-hydroxytamoxifen (4-HT) by fusing the Cas9 enzyme with the hormone-binding domain of the estrogen receptor (ERT2). The final optimized variant, termed iCas, showed low endonuclease activity without 4-HT but high editing efficiency at multiple loci with the chemical. We also tuned the duration and concentration of 4-HT treatment to reduce off-target genome modification. Additionally, we benchmarked iCas against other chemical-inducible methods and found that it had the fastest on rate and that its activity could be toggled on and off repeatedly. Collectively, these results highlight the utility of iCas for rapid and reversible control of genome-editing function.
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http://dx.doi.org/10.1038/nchembio.2179DOI Listing
November 2016