The Experts below are selected from a list of 59907 Experts worldwide ranked by ideXlab platform
Haibo Zhou - One of the best experts on this subject based on the ideXlab platform.
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off target RNA Mutation induced by dna base editing and its elimination by mutagenesis
Nature, 2019Co-Authors: Changyang Zhou, Rong Zeng, Yidi Sun, Rui Yan, Yajing Liu, Erwei Zuo, Linxiao Han, Yu Wei, Haibo ZhouAbstract:Recently developed DNA base editing methods enable the direct generation of desired point Mutations in genomic DNA without generating any double-strand breaks1-3, but the issue of off-target edits has limited the application of these methods. Although several previous studies have evaluated off-target Mutations in genomic DNA4-8, it is now clear that the deaminases that are integral to commonly used DNA base editors often bind to RNA9-13. For example, the cytosine deaminase APOBEC1-which is used in cytosine base editors (CBEs)-targets both DNA and RNA12, and the adenine deaminase TadA-which is used in adenine base editors (ABEs)-induces site-specific inosine formation on RNA9,11. However, any potential RNA Mutations caused by DNA base editors have not been evaluated. Adeno-associated viruses are the most common delivery system for gene therapies that involve DNA editing; these viruses can sustain long-term gene expression in vivo, so the extent of potential RNA Mutations induced by DNA base editors is of great concern14-16. Here we quantitatively evaluated RNA single nucleotide variations (SNVs) that were induced by CBEs or ABEs. Both the cytosine base editor BE3 and the adenine base editor ABE7.10 generated tens of thousands of off-target RNA SNVs. Subsequently, by engineering deaminases, we found that three CBE variants and one ABE variant showed a reduction in off-target RNA SNVs to the baseline while maintaining efficient DNA on-target activity. This study reveals a previously overlooked aspect of off-target effects in DNA editing and also demonstrates that such effects can be eliminated by engineering deaminases.
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off target RNA Mutation induced by dna base editing and its elimination by mutagenesis
Nature, 2019Co-Authors: Changyang Zhou, Chan Gu, Xinde Hu, Yixue Li, Rong Zeng, Haibo Zhou, Hui YangAbstract:Recently developed DNA base editing methods enable the direct generation of desired point Mutations in genomic DNA without generating any double-strand breaks1–3, but the issue of off-target edits has limited the application of these methods. Although several previous studies have evaluated off-target Mutations in genomic DNA4–8, it is now clear that the deaminases that are integral to commonly used DNA base editors often bind to RNA9–13. For example, the cytosine deaminase APOBEC1—which is used in cytosine base editors (CBEs)—targets both DNA and RNA12, and the adenine deaminase TadA—which is used in adenine base editors (ABEs)—induces site-specific inosine formation on RNA9,11. However, any potential RNA Mutations caused by DNA base editors have not been evaluated. Adeno-associated viruses are the most common delivery system for gene therapies that involve DNA editing; these viruses can sustain long-term gene expression in vivo, so the extent of potential RNA Mutations induced by DNA base editors is of great concern14–16. Here we quantitatively evaluated RNA single nucleotide variations (SNVs) that were induced by CBEs or ABEs. Both the cytosine base editor BE3 and the adenine base editor ABE7.10 generated tens of thousands of off-target RNA SNVs. Subsequently, by engineering deaminases, we found that three CBE variants and one ABE variant showed a reduction in off-target RNA SNVs to the baseline while maintaining efficient DNA on-target activity. This study reveals a previously overlooked aspect of off-target effects in DNA editing and also demonstrates that such effects can be eliminated by engineering deaminases. Cytosine and adenine base editors have undesired off-target effects on RNA, but this activity can be reduced in deaminase-engineered variants while preserving on-target DNA editing.
Changyang Zhou - One of the best experts on this subject based on the ideXlab platform.
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off target RNA Mutation induced by dna base editing and its elimination by mutagenesis
Nature, 2019Co-Authors: Changyang Zhou, Rong Zeng, Yidi Sun, Rui Yan, Yajing Liu, Erwei Zuo, Linxiao Han, Yu Wei, Haibo ZhouAbstract:Recently developed DNA base editing methods enable the direct generation of desired point Mutations in genomic DNA without generating any double-strand breaks1-3, but the issue of off-target edits has limited the application of these methods. Although several previous studies have evaluated off-target Mutations in genomic DNA4-8, it is now clear that the deaminases that are integral to commonly used DNA base editors often bind to RNA9-13. For example, the cytosine deaminase APOBEC1-which is used in cytosine base editors (CBEs)-targets both DNA and RNA12, and the adenine deaminase TadA-which is used in adenine base editors (ABEs)-induces site-specific inosine formation on RNA9,11. However, any potential RNA Mutations caused by DNA base editors have not been evaluated. Adeno-associated viruses are the most common delivery system for gene therapies that involve DNA editing; these viruses can sustain long-term gene expression in vivo, so the extent of potential RNA Mutations induced by DNA base editors is of great concern14-16. Here we quantitatively evaluated RNA single nucleotide variations (SNVs) that were induced by CBEs or ABEs. Both the cytosine base editor BE3 and the adenine base editor ABE7.10 generated tens of thousands of off-target RNA SNVs. Subsequently, by engineering deaminases, we found that three CBE variants and one ABE variant showed a reduction in off-target RNA SNVs to the baseline while maintaining efficient DNA on-target activity. This study reveals a previously overlooked aspect of off-target effects in DNA editing and also demonstrates that such effects can be eliminated by engineering deaminases.
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off target RNA Mutation induced by dna base editing and its elimination by mutagenesis
Nature, 2019Co-Authors: Changyang Zhou, Chan Gu, Xinde Hu, Yixue Li, Rong Zeng, Haibo Zhou, Hui YangAbstract:Recently developed DNA base editing methods enable the direct generation of desired point Mutations in genomic DNA without generating any double-strand breaks1–3, but the issue of off-target edits has limited the application of these methods. Although several previous studies have evaluated off-target Mutations in genomic DNA4–8, it is now clear that the deaminases that are integral to commonly used DNA base editors often bind to RNA9–13. For example, the cytosine deaminase APOBEC1—which is used in cytosine base editors (CBEs)—targets both DNA and RNA12, and the adenine deaminase TadA—which is used in adenine base editors (ABEs)—induces site-specific inosine formation on RNA9,11. However, any potential RNA Mutations caused by DNA base editors have not been evaluated. Adeno-associated viruses are the most common delivery system for gene therapies that involve DNA editing; these viruses can sustain long-term gene expression in vivo, so the extent of potential RNA Mutations induced by DNA base editors is of great concern14–16. Here we quantitatively evaluated RNA single nucleotide variations (SNVs) that were induced by CBEs or ABEs. Both the cytosine base editor BE3 and the adenine base editor ABE7.10 generated tens of thousands of off-target RNA SNVs. Subsequently, by engineering deaminases, we found that three CBE variants and one ABE variant showed a reduction in off-target RNA SNVs to the baseline while maintaining efficient DNA on-target activity. This study reveals a previously overlooked aspect of off-target effects in DNA editing and also demonstrates that such effects can be eliminated by engineering deaminases. Cytosine and adenine base editors have undesired off-target effects on RNA, but this activity can be reduced in deaminase-engineered variants while preserving on-target DNA editing.
Ramesh V Sonti - One of the best experts on this subject based on the ideXlab platform.
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xanthomonas oryzae pv oryzae exoribonuclease r is required for complete virulence in rice optimal motility and growth under stress
Phytopathology, 2021Co-Authors: Sharmila Roy, Pragya Mittal, Lavanya Tayi, Sahitya Bondada, M K Ray, Hitendra Kumar Patel, Ramesh V SontiAbstract:Exoribonuclease R (RNAse R) is a 3’ hydrolytic exoribonuclease that can degrade structured RNA. Mutation in RNAse R affects virulence of certain human pathogenic bacteria. The aim of this study was...
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xanthomonas oryzae pv exoribonuclease r is required for complete virulence in rice optimal motility and growth under stress
Phytopathology, 2021Co-Authors: Sharmila Roy, Pragya Mittal, Lavanya Tayi, Sahitya Bondada, M K Ray, Hitendra Kumar Patel, Ramesh V SontiAbstract:Exoribonuclease R (RNAse R) is a 3' hydrolytic exoribonuclease that can degrade structured RNA. Mutation in RNAse R affects virulence of certain human pathogenic bacteria. The aim of this study was to determine whether RNAse R is required for virulence of the phytopathogen that causes bacterial blight in rice, Xanthomonas oryzae pv. oryzae (Xoo). In silico analysis has indicated that RNAse R is highly conserved among various Xanthomonads. Amino acid sequence alignment of Xoo RNAse R with RNAse R from various taxa indicated that Xoo RNAse R clustered with RNAse R of order Xanthomonadales. In order to study its role in virulence, a gene disruption mutant of Xoo RNAse R (rnr -) was generated. The Xoo rnr - mutant is moderately virulence deficient and the complementing strain (rnr -/pHM1::rnr) rescued the virulence deficiency of the mutant. We investigated swimming and swarming motilities in both nutrient deficient minimal and nutrient optimal media. We observed that rnr - mutant has adversely affected the swimming and swarming motilities of Xoo in optimal media. However, in nutrient deficient media only swimming motility was noticeably affected. Growth curves in optimal media at suboptimal temperature (15°C, cold stress) indicate that Xoo rnr - mutant grows slower than Xoo wild type (wt) and complementing strain (rnr -/pHM1::rnr). Taken together, we report for the first time that RNAse R function is necessary for complete virulence of Xoo in rice. It is also important for motility of Xoo in media and for growth of Xoo at suboptimal temperature.
Hui Yang - One of the best experts on this subject based on the ideXlab platform.
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off target RNA Mutation induced by dna base editing and its elimination by mutagenesis
Nature, 2019Co-Authors: Changyang Zhou, Chan Gu, Xinde Hu, Yixue Li, Rong Zeng, Haibo Zhou, Hui YangAbstract:Recently developed DNA base editing methods enable the direct generation of desired point Mutations in genomic DNA without generating any double-strand breaks1–3, but the issue of off-target edits has limited the application of these methods. Although several previous studies have evaluated off-target Mutations in genomic DNA4–8, it is now clear that the deaminases that are integral to commonly used DNA base editors often bind to RNA9–13. For example, the cytosine deaminase APOBEC1—which is used in cytosine base editors (CBEs)—targets both DNA and RNA12, and the adenine deaminase TadA—which is used in adenine base editors (ABEs)—induces site-specific inosine formation on RNA9,11. However, any potential RNA Mutations caused by DNA base editors have not been evaluated. Adeno-associated viruses are the most common delivery system for gene therapies that involve DNA editing; these viruses can sustain long-term gene expression in vivo, so the extent of potential RNA Mutations induced by DNA base editors is of great concern14–16. Here we quantitatively evaluated RNA single nucleotide variations (SNVs) that were induced by CBEs or ABEs. Both the cytosine base editor BE3 and the adenine base editor ABE7.10 generated tens of thousands of off-target RNA SNVs. Subsequently, by engineering deaminases, we found that three CBE variants and one ABE variant showed a reduction in off-target RNA SNVs to the baseline while maintaining efficient DNA on-target activity. This study reveals a previously overlooked aspect of off-target effects in DNA editing and also demonstrates that such effects can be eliminated by engineering deaminases. Cytosine and adenine base editors have undesired off-target effects on RNA, but this activity can be reduced in deaminase-engineered variants while preserving on-target DNA editing.
Yidi Sun - One of the best experts on this subject based on the ideXlab platform.
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off target RNA Mutation induced by dna base editing and its elimination by mutagenesis
Nature, 2019Co-Authors: Changyang Zhou, Rong Zeng, Yidi Sun, Rui Yan, Yajing Liu, Erwei Zuo, Linxiao Han, Yu Wei, Haibo ZhouAbstract:Recently developed DNA base editing methods enable the direct generation of desired point Mutations in genomic DNA without generating any double-strand breaks1-3, but the issue of off-target edits has limited the application of these methods. Although several previous studies have evaluated off-target Mutations in genomic DNA4-8, it is now clear that the deaminases that are integral to commonly used DNA base editors often bind to RNA9-13. For example, the cytosine deaminase APOBEC1-which is used in cytosine base editors (CBEs)-targets both DNA and RNA12, and the adenine deaminase TadA-which is used in adenine base editors (ABEs)-induces site-specific inosine formation on RNA9,11. However, any potential RNA Mutations caused by DNA base editors have not been evaluated. Adeno-associated viruses are the most common delivery system for gene therapies that involve DNA editing; these viruses can sustain long-term gene expression in vivo, so the extent of potential RNA Mutations induced by DNA base editors is of great concern14-16. Here we quantitatively evaluated RNA single nucleotide variations (SNVs) that were induced by CBEs or ABEs. Both the cytosine base editor BE3 and the adenine base editor ABE7.10 generated tens of thousands of off-target RNA SNVs. Subsequently, by engineering deaminases, we found that three CBE variants and one ABE variant showed a reduction in off-target RNA SNVs to the baseline while maintaining efficient DNA on-target activity. This study reveals a previously overlooked aspect of off-target effects in DNA editing and also demonstrates that such effects can be eliminated by engineering deaminases.
