Article
Genetics & Heredity
Emily Yang, Matthew Metzloff, Anna M. Langmueller, Xuejiao Xu, Andrew G. Clark, Philipp W. Messer, Jackson Champer
Summary: Gene drives are engineered alleles that can bias inheritance and spread throughout a population. This study constructed a homing suppression drive in Drosophila melanogaster using multiplexed gRNAs to inhibit the formation of resistance alleles, reaching a moderate equilibrium frequency in cage populations but with a fitness cost preventing elimination. The results demonstrate the viability of the multiplexed gRNAs strategy in homing suppression gene drives.
G3-GENES GENOMES GENETICS
(2022)
Article
Biotechnology & Applied Microbiology
Alexander Nash, Paolo Capriotti, Astrid Hoermann, Phillipos Aris Papathanos, Nikolai Windbichler
Summary: The research team explored the minimal genetic components needed to constitute autonomous gene drives in fruit flies, and designed the rcd-1r(d) allele which supports efficient gene drive. Such simple integral gene drives could enable the modularization of drive and effector functions.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Amarish K. Yadav, Cole Butler, Akihiko Yamamoto, Anandrao A. Patil, Alun L. Lloyd, Maxwell J. Scott
Summary: Genetic-based methods, such as CRISPR homing gene drives, offer efficient and cost-effective ways to control insect pests. In this study, split homing drives targeting the dsx gene in Drosophila suzukii were developed and evaluated. The modified drive showed high transmission rates and could potentially be used for effective control of D. suzukii populations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Medicine, Research & Experimental
Xi Xiang, Xiaoying Zhao, Xiaoguang Pan, Zhanying Dong, Jiaying Yu, Siyuan Li, Xue Liang, Peng Han, Kunli Qu, Jonas Brorson Jensen, Jean Farup, Fei Wang, Trine Skov Petersen, Lars Bolund, Huajing Teng, Lin Lin, Yonglun Luo
Summary: CRISPR gene therapy shows promise for treating DMD by restoring dystrophin expression through efficient gene editing strategies. The successful correction of mutations and induction of myotubes in cells may provide a valuable therapeutic approach for DMD treatment.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2021)
Article
Biology
Samuel E. Champer, Isabel K. Kim, Andrew G. Clark, Philipp W. Messer, Jackson Champer
Summary: Recent experiments have shown the effectiveness of gene drives in suppressing mosquito populations to combat malaria. However, the combination of a homing drive and an X-shredder element was found to be less effective than expected, while drives based on the nos promoter may be more promising.
Article
Biology
Matthew Metzloff, Emily Yang, Sumit Dhole, Andrew G. Clark, Philipp W. Messer, Jackson Champer
Summary: Our study demonstrates the construction of a tethered drive system in Drosophila, utilizing a locally confined CRISPR Toxin-Antidote Recessive Embryo (TARE) drive to support modification and suppression homing drives. Each drive was able to bias inheritance in its favor, and the TARE drive was shown to spread only when released above a threshold frequency in experimental cage populations. After the TARE drive had established in the population, it facilitated the spread of a subsequently released split homing modification drive (to all individuals in the cage) and of a homing suppression drive (to its equilibrium frequency).
Article
Biology
Yiran Liu, Jackson Champer
Summary: Gene drives have the potential to effectively suppress haplodiploid populations. A drive targeting female fertility gene has been found to be successful, although it is less powerful compared to diploids and more susceptible to resistance alleles.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Sara Sanz Juste, Emily M. Okamoto, Christina Nguyen, Xuechun Feng, Victor Lopez Del Amo
Summary: One method for reducing the impact of vector-borne diseases is through the use of CRISPR-based gene drives. The authors present a proof-of-concept gene-drive system driven by Cas12a that can be regulated via temperature modulation, and also demonstrate the capability of building double gene drives by combining Cas9 and Cas12a.
NATURE COMMUNICATIONS
(2023)
Article
Agriculture, Multidisciplinary
Muniba Abid Munir Malik, Muhammad Saleem Haider, Ying Zhai, Muhammad Azmat Ullah Khan, Hanu R. Pappu
Summary: This study demonstrates the potential of using the Cas9-based genome editing technique to generate resistance against CpCDV. Multiple gRNA constructs targeting conserved genomic regions were successful in triggering resistance in tobacco and tomato plants. One multiplex construct targeting three genomic regions showed a significant decrease in viral titre, while other constructs and individual sgRNAs did not produce consistent results.
JOURNAL OF PLANT DISEASES AND PROTECTION
(2023)
Review
Biotechnology & Applied Microbiology
Pratima R. Chennuri, Zach N. Adelman, Kevin M. Myles
Summary: This review summarizes the current state of the art in the development of technologies to prevent the uncontrolled spread of CRISPR-based autonomous homing gene drives.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Sebald A. N. Verkuijl, Joshua X. D. Ang, Luke Alphey, Michael B. Bonsall, Michelle A. E. Anderson
Summary: This article discusses the use of genetic changes to address ecological and public health challenges caused by insect pests. It highlights the development of technologies such as synthetic gene drives and the recent advancements in programmable nucleases like CRISPR-Cas9. The focus is on homing endonuclease gene drives and the challenges involved, as well as strategies to improve their efficiency and mitigate unintended outcomes.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Immunology
Chong-Han Chung, Alexander G. Allen, Andrew Atkins, Robert W. Link, Michael R. Nonnemacher, Will Dampier, Brian Wigdahl
Summary: CRISPR-mediated HIV-1 genome editing shows promising outcomes, but existing sequence variants reduce efficiency. By considering global patient and subtype coverage, researchers identified novel gRNAs targeting critical functional regions. Broad-spectrum gRNAs are essential for developing generalizable CRISPR-based HIV-1 therapy.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Review
Geriatrics & Gerontology
Jingyu Yu, Tianwen Li, Jianhong Zhu
Summary: This article discusses the importance and potential of gene therapy technology in treating aging or age-related chronic diseases. Although effective methods are still lacking, the study of genes related to aging represents a promising research direction that has already achieved significant breakthroughs.
Article
Biochemical Research Methods
Kok Zhi Lee, Michael A. Mechikoff, Mrugesh Krishna Parasa, Tyler J. Rankin, Paula Pandolfi, Kevin S. Fitzgerald, Ethan T. Hillman, Kevin Solomon
Summary: Prokaryote genomes encode diverse programmable DNA endonucleases with significant potential for biotechnology and gene editing. A positive selection screen based on the homing endonuclease I-SceI has been developed and validated to measure the relative activity of endonucleases and enrich for more active variants. This system may be applied in high throughput to characterize novel programmable endonucleases and evolve endonuclease function.
ACS SYNTHETIC BIOLOGY
(2022)
Review
Immunology
Alexander Biederstaedt, Gohar Shahwar Manzar, May Daher
Summary: The advent of cellular immunotherapy and precision genome editing has revolutionized cancer treatment, offering new possibilities but also facing certain limitations. Various engineering strategies are being increasingly utilized to overcome present constraints in building more potent cellular therapeutics.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Iskander Said, Michael P. McGurk, Andrew G. Clark, Daniel A. Barbash
Summary: Competition between transposable elements (TEs) may lead to the emergence of new variants, with hosts preferentially producing antisense piRNAs to silence these emerging variants.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Biology
Manisha Munasinghe, Benjamin C. Haller, Andrew G. Clark
Summary: In this study, the consequences of sexually antagonistic mitochondrial-nuclear interactions in a subdivided population were investigated using computer simulations. Disrupting these interactions resulted in less-fit males, but the strength of these interactions was not enough to drive population isolation.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2022)
Article
Biology
Matthew Metzloff, Emily Yang, Sumit Dhole, Andrew G. Clark, Philipp W. Messer, Jackson Champer
Summary: Our study demonstrates the construction of a tethered drive system in Drosophila, utilizing a locally confined CRISPR Toxin-Antidote Recessive Embryo (TARE) drive to support modification and suppression homing drives. Each drive was able to bias inheritance in its favor, and the TARE drive was shown to spread only when released above a threshold frequency in experimental cage populations. After the TARE drive had established in the population, it facilitated the spread of a subsequently released split homing modification drive (to all individuals in the cage) and of a homing suppression drive (to its equilibrium frequency).
Article
Evolutionary Biology
Tram N. Nguyen, Nancy Chen, Elissa J. Cosgrove, Reed Bowman, John W. Fitzpatrick, Andrew G. Clark
Summary: Understanding the genomic consequences of population decline is crucial for predicting species' vulnerability to global change. This study compared the genetic diversity, inbreeding, relatedness, and lengths of runs of homozygosity (ROH) between two subpopulations of Florida scrub jays that have experienced different demographic trajectories. The results showed that the population decline led to decreased heterozygosity and increased inbreeding in the declining population, while the stable population did not show significant changes. This study highlights the divergence in genetic characteristics caused by local population decline despite ongoing gene flow.
EVOLUTIONARY APPLICATIONS
(2022)
Article
Neurosciences
You Chen, Andrew G. Clark, Haiyuan Yu
Summary: This article presents a fine-mapping approach called RefMap, which integrates functional genomics with GWAS summary statistics to prioritize causal variants for amyotrophic lateral sclerosis.
Article
Multidisciplinary Sciences
Felicia N. New, Benjamin R. Baer, Andrew G. Clark, Martin T. Wells, Ilana L. Brito
Summary: This study examines the interactions between host genetics and gut microbiome by analyzing the gut microbiomes and human variants of 250 individuals. The findings reveal associations between host genetics and microbiome-related metabolic traits, disorders, and certain cancers. The study also identifies common and rare microbial functions that are associated with host genetics.
SCIENTIFIC REPORTS
(2022)
Article
Genetics & Heredity
Emily Yang, Matthew Metzloff, Anna M. Langmueller, Xuejiao Xu, Andrew G. Clark, Philipp W. Messer, Jackson Champer
Summary: Gene drives are engineered alleles that can bias inheritance and spread throughout a population. This study constructed a homing suppression drive in Drosophila melanogaster using multiplexed gRNAs to inhibit the formation of resistance alleles, reaching a moderate equilibrium frequency in cage populations but with a fitness cost preventing elimination. The results demonstrate the viability of the multiplexed gRNAs strategy in homing suppression gene drives.
G3-GENES GENOMES GENETICS
(2022)
Article
Multidisciplinary Sciences
Yiqin Wang, Xiaoxian Guo, Xiumei Hong, Guoying Wang, Colleen Pearson, Barry Zuckerman, Andrew G. Clark, Kimberly O. O'Brien, Xiaobin Wang, Zhenglong Gu
Summary: This study investigates the role of mitochondrial genome (mtDNA) in autism spectrum disorder (ASD) risk, and finds that mutations in mtDNA are associated with increased ASD risk in children, and the heteroplasmies in parents have different effects in ASD children.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Anna M. Langmueller, Jackson Champer, Sandra Lapinska, Lin Xie, Matthew Metzloff, Samuel E. Champer, Jingxian Liu, Yineng Xu, Jie Du, Andrew G. Clark, Philipp W. Messer
Summary: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 is a highly efficient genome editing technology with a wide range of potential applications. However, integrating CRISPR/Cas9 into an organism's genome may have harmful effects on transgenic individuals, particularly in the case of gene drives that aim to alter the genetics of entire populations. This study assesses the fitness effects of CRISPR/Cas9 expression in Drosophila melanogaster populations, and finds that a high-fidelity version of Cas9 performs well in terms of drive conversion efficiency. These findings have implications for the design of gene drives and other applications involving genomic integration of CRISPR endonucleases.
Article
Biology
Samuel E. Champer, Isabel K. Kim, Andrew G. Clark, Philipp W. Messer, Jackson Champer
Summary: Recent experiments have shown the effectiveness of gene drives in suppressing mosquito populations to combat malaria. However, the combination of a homing drive and an X-shredder element was found to be less effective than expected, while drives based on the nos promoter may be more promising.
Article
Biochemistry & Molecular Biology
Wenqi Cao, Kory C. Douglas, Paul B. Samollow, John L. VandeBerg, Xu Wang, Andrew G. Clark
Summary: Genomic imprinting is a phenomenon that plays important roles in many biological processes, and is only observed in therian mammals. A study investigated the imprinting pattern in marsupials using unbiased RNA-seq studies, discovering and validating 13 imprinted genes, including nine novel imprinted genes. Differential methylation and clustering were observed at marsupial-specific imprinted genes, revealing common mechanisms in the epigenetic regulation of marsupial imprinting.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Multidisciplinary Sciences
Sofie Y. N. Delbare, Sara Venkatraman, Kate Scuderi, Martin T. Wells, Mariana F. Wolfner, Sumanta Basu, Andrew G. Clark
Summary: This study used high-resolution time series RNA-sequencing data to explore the genetic architecture of female's response to SP in Drosophila melanogaster. The results showed that SP not only triggers the transcriptional switch in females after mating, but also affects metabolic gene regulatory network and neuronal gene regulatory network, especially the disruption of female's circadian rhythm.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Genetics & Heredity
Jullien M. Flynn, Kevin B. Hu, Andrew G. Clark
Summary: This study discovered chromosome fusion and fission events in a strain of D. virilis, leading to genome instability. One substrain with an X-autosome fusion had a 20x higher nondisjunction rate and another substrain with higher satellite DNA had an overall higher DNA breakage rate. These findings suggest a potential role of satellite DNA abundance in genome instability. The establishment of a novel system with four different karyotypes provides a valuable tool for future studies on genome instability, centromere function, and sex chromosome evolution.
Article
Ecology
Jaehee Kim, Keith D. Harris, Isabel K. Kim, Shahar Shemesh, Philipp W. Messer, Gili Greenbaum
Summary: Gene drive technology is a promising tool in fighting vector-borne diseases, agricultural pests, and invasive species. It is important to incorporate ecological features into gene drive models and evaluate its dynamics, potential outcomes, and risks realistically.
Article
Biochemistry & Molecular Biology
Anna C. Clark, Rey Edison, Kevin Esvelt, Sebastian Kamau, Ludovic Dutoit, Jackson Champer, Samuel E. Champer, Philipp W. Messer, Alana Alexander, Neil J. Gemmell
Summary: This manuscript introduces a framework for identifying and evaluating target genes based on biological gene function, gene expression, and results from mouse knockout models. The framework identifies 16 genes essential for male fertility and 12 genes important for female fertility that may be feasible targets for mammalian gene drives and other genetic pest control technologies.
MOLECULAR ECOLOGY RESOURCES
(2023)
