The scientific community is continuously working to translate the novel biomedical techniques into effective medical treatments.CRISPR-Cas9 system(Clustered Regularly Interspaced Short Palindromic Repeats-9),commonly ...The scientific community is continuously working to translate the novel biomedical techniques into effective medical treatments.CRISPR-Cas9 system(Clustered Regularly Interspaced Short Palindromic Repeats-9),commonly known as the“molecular scissor”,represents a recently developed biotechnology able to improve the quality and the efficacy of traditional treatments,related to several human diseases,such as chronic diseases,neurodegenerative pathologies and,interestingly,oral diseases.Of course,dental medicine has notably increased the use of biotechnologies to ensure modern and conservative approaches:in this landscape,the use of CRISPR-Cas9 system may speed and personalize the traditional therapies,ensuring a good predictability of clinical results.The aim of this critical overview is to provide evidence on CRISPR efficacy,taking into specific account its applications in oral medicine.展开更多
The advancement of Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)gene editing technology has revolutionized the comprehension of human genome,propelling molecular and cellular biology research into ...The advancement of Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)gene editing technology has revolutionized the comprehension of human genome,propelling molecular and cellular biology research into unexplored realms and accelerating progress in life sciences and medicine.CRISPR-based gene screening,recognized for its efficiency and practicality,is widely utilized across diverse biological fields.Aging is a multifaceted process governed by a myriad of genetic and epigenetic factors.Unraveling the genes regulating aging holds promise for understanding this intricate phenomenon and devising strategies for its assessment and intervention.This review provides a comprehensive overview of the progress in CRISPR screening and its applications in aging research,while also offering insights into future directions.CRISPR-based genetic-manipulation tools are positioned as indispensable instruments for mitigating aging and managing age-related diseases.展开更多
Orphan diseases are rare diseases that affect less than 200000 individuals within the United States.Most orphan diseases are of neurologic and genetic origin.With the current advances in technology,more funding has be...Orphan diseases are rare diseases that affect less than 200000 individuals within the United States.Most orphan diseases are of neurologic and genetic origin.With the current advances in technology,more funding has been devoted to developing therapeutic agents for patients with these conditions.In our review,we highlight emerging options for patients with neurologic orphan diseases,specifically including diseases resulting in muscular deterioration,epilepsy,seizures,neurodegenerative movement disorders,inhibited cognitive development,neuron deterioration,and tumors.After extensive literature review,gene therapy offers a promising route for the treatment of neurologic orphan diseases.The use of clustered regularly interspaced palindromic repeats/Cas9 has demonstrated positive results in experiments investigating its role in several diseases.Additionally,the use of adeno-associated viral vectors has shown improvement in survival,motor function,and developmental milestones,while also demonstrating reversal of sensory ataxia and cardiomyopathy in Friedreich ataxia patients.Antisense oligonucleotides have also been used in some neurologic orphan diseases with positive outcomes.Mammalian target of rapamycin inhibitors are currently being investigated and have reduced abnormal cell growth,proliferation,and angiogenesis.Emerging innovations and the role of genetic treatments open a new window of opportunity for the treatment of neurologic orphan diseases.展开更多
Pancreatic cancer(PC)remains one of the most challenging diseases,with a very poor 5-year overall survival of around 11.5%.Kirsten rat sarcoma virus(KRAS)mutation is seen in 90%-95%of PC patients and plays an importan...Pancreatic cancer(PC)remains one of the most challenging diseases,with a very poor 5-year overall survival of around 11.5%.Kirsten rat sarcoma virus(KRAS)mutation is seen in 90%-95%of PC patients and plays an important role in cancer cell proliferation,differentiation,metabolism,and survival,making it an essential mutation for targeted therapy.Despite extensive efforts in studying this oncogene,there has been little success in finding a drug to target this pathway,labelling it for decades as“undruggable”.In this article we summarize some of the efforts made to target the KRAS pathway in PC,discuss the challenges,and shed light on promising clinical trials.展开更多
Hepatocyte nuclear factor 1 alpha(HNF1A),hepatocyte nuclear factor 4 alpha(HNF4A),and forkhead box protein A2(FOXA2)are key transcription factors that regulate a complex gene network in the liver,cre-ating a regulator...Hepatocyte nuclear factor 1 alpha(HNF1A),hepatocyte nuclear factor 4 alpha(HNF4A),and forkhead box protein A2(FOXA2)are key transcription factors that regulate a complex gene network in the liver,cre-ating a regulatory transcriptional loop.The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes.Our in silico analysis of HNF1A,HNF4A.and FOXA2 binding to the ten candidate glyco-genes studied in this work confirms a significant enrich-ment of these transcription factors specifically in the liver.Our previous studies identified HNF1A as a master regulator of fucosylation,glycan branching,and galactosylation of plasma glycoproteins.Here,we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype.We used the state-of-the-art clus-tered regularly interspaced short palindromic repeats/dead Cas9(CRISPR/dCas9)molecular tool for the downregulation of the HNF1A,HNF4A,and FOXA2 genes in HepG2 cells-a human liver cancer cell line.The results show that the downregulation of all three genes individually and in pairs affects the transcrip-tional activity of many glyco-genes,although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures.The effect is better seen as an overall change in the total HepG2 N-glycome,primarily due to the extension of biantennary glycans.We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure.We also propose a model showing feedback loops with the mutual activation of HNF1A-FOXA2 and HNF4A-FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.展开更多
BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental condition characterized by heterogeneous symptoms and genetic underpinnings.Recent advancements in genetic and epigenetic research have provided ...BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental condition characterized by heterogeneous symptoms and genetic underpinnings.Recent advancements in genetic and epigenetic research have provided insights into the intricate mechanisms contributing to ASD,influencing both diagnosis and therapeutic strategies.AIM To explore the genetic architecture of ASD,elucidate mechanistic insights into genetic mutations,and examine gene-environment interactions.METHODS A comprehensive systematic review was conducted,integrating findings from studies on genetic variations,epigenetic mechanisms(such as DNA methylation and histone modifications),and emerging technologies[including Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)-Cas9 and single-cell RNA sequencing].Relevant articles were identified through systematic searches of databases such as PubMed and Google Scholar.RESULTS Genetic studies have identified numerous risk genes and mutations associated with ASD,yet many cases remain unexplained by known factors,suggesting undiscovered genetic components.Mechanistic insights into how these genetic mutations impact neural development and brain connectivity are still evolving.Epigenetic modifications,particularly DNA methylation and non-coding RNAs,also play significant roles in ASD pathogenesis.Emerging technologies like CRISPR-Cas9 and advanced bioinformatics are advancing our understanding by enabling precise genetic editing and analysis of complex genomic data.CONCLUSION Continued research into the genetic and epigenetic underpinnings of ASD is crucial for developing personalized and effective treatments.Collaborative efforts integrating multidisciplinary expertise and international collaborations are essential to address the complexity of ASD and translate genetic discoveries into clinical practice.Addressing unresolved questions and ethical considerations surrounding genetic research will pave the way for improved diagnostic tools and targeted therapies,ultimately enhancing outcomes for individuals affected by ASD.展开更多
文摘The scientific community is continuously working to translate the novel biomedical techniques into effective medical treatments.CRISPR-Cas9 system(Clustered Regularly Interspaced Short Palindromic Repeats-9),commonly known as the“molecular scissor”,represents a recently developed biotechnology able to improve the quality and the efficacy of traditional treatments,related to several human diseases,such as chronic diseases,neurodegenerative pathologies and,interestingly,oral diseases.Of course,dental medicine has notably increased the use of biotechnologies to ensure modern and conservative approaches:in this landscape,the use of CRISPR-Cas9 system may speed and personalize the traditional therapies,ensuring a good predictability of clinical results.The aim of this critical overview is to provide evidence on CRISPR efficacy,taking into specific account its applications in oral medicine.
文摘The advancement of Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)gene editing technology has revolutionized the comprehension of human genome,propelling molecular and cellular biology research into unexplored realms and accelerating progress in life sciences and medicine.CRISPR-based gene screening,recognized for its efficiency and practicality,is widely utilized across diverse biological fields.Aging is a multifaceted process governed by a myriad of genetic and epigenetic factors.Unraveling the genes regulating aging holds promise for understanding this intricate phenomenon and devising strategies for its assessment and intervention.This review provides a comprehensive overview of the progress in CRISPR screening and its applications in aging research,while also offering insights into future directions.CRISPR-based genetic-manipulation tools are positioned as indispensable instruments for mitigating aging and managing age-related diseases.
文摘Orphan diseases are rare diseases that affect less than 200000 individuals within the United States.Most orphan diseases are of neurologic and genetic origin.With the current advances in technology,more funding has been devoted to developing therapeutic agents for patients with these conditions.In our review,we highlight emerging options for patients with neurologic orphan diseases,specifically including diseases resulting in muscular deterioration,epilepsy,seizures,neurodegenerative movement disorders,inhibited cognitive development,neuron deterioration,and tumors.After extensive literature review,gene therapy offers a promising route for the treatment of neurologic orphan diseases.The use of clustered regularly interspaced palindromic repeats/Cas9 has demonstrated positive results in experiments investigating its role in several diseases.Additionally,the use of adeno-associated viral vectors has shown improvement in survival,motor function,and developmental milestones,while also demonstrating reversal of sensory ataxia and cardiomyopathy in Friedreich ataxia patients.Antisense oligonucleotides have also been used in some neurologic orphan diseases with positive outcomes.Mammalian target of rapamycin inhibitors are currently being investigated and have reduced abnormal cell growth,proliferation,and angiogenesis.Emerging innovations and the role of genetic treatments open a new window of opportunity for the treatment of neurologic orphan diseases.
文摘Pancreatic cancer(PC)remains one of the most challenging diseases,with a very poor 5-year overall survival of around 11.5%.Kirsten rat sarcoma virus(KRAS)mutation is seen in 90%-95%of PC patients and plays an important role in cancer cell proliferation,differentiation,metabolism,and survival,making it an essential mutation for targeted therapy.Despite extensive efforts in studying this oncogene,there has been little success in finding a drug to target this pathway,labelling it for decades as“undruggable”.In this article we summarize some of the efforts made to target the KRAS pathway in PC,discuss the challenges,and shed light on promising clinical trials.
基金the European Structural and Investment Funded Grant"Cardio Metabolic"(#KK.01.2.1.02.0321)the Croatian National Centre of Research Excellence in Personalized Healthcare Grant(#KK.01.1.1.01.0010)+2 种基金the European Regional Development Fund Grant,project"CRISPR/Cas9-CasMouse"(#KK.01.1.1.04.0085)the European Structural and Investment Funded Project of Centre of Competence in Molecular Diagnostics(#KK.01.2.2.03.0006)the Croatian National Centre of Research Excellence in Personalized Healthcare Grant(#KK.01.1.1.01.0010).
文摘Hepatocyte nuclear factor 1 alpha(HNF1A),hepatocyte nuclear factor 4 alpha(HNF4A),and forkhead box protein A2(FOXA2)are key transcription factors that regulate a complex gene network in the liver,cre-ating a regulatory transcriptional loop.The Encode and ChIP-Atlas databases identify the recognition sites of these transcription factors in many glycosyltransferase genes.Our in silico analysis of HNF1A,HNF4A.and FOXA2 binding to the ten candidate glyco-genes studied in this work confirms a significant enrich-ment of these transcription factors specifically in the liver.Our previous studies identified HNF1A as a master regulator of fucosylation,glycan branching,and galactosylation of plasma glycoproteins.Here,we aimed to functionally validate the role of the three transcription factors on downstream glyco-gene transcriptional expression and the possible effect on glycan phenotype.We used the state-of-the-art clus-tered regularly interspaced short palindromic repeats/dead Cas9(CRISPR/dCas9)molecular tool for the downregulation of the HNF1A,HNF4A,and FOXA2 genes in HepG2 cells-a human liver cancer cell line.The results show that the downregulation of all three genes individually and in pairs affects the transcrip-tional activity of many glyco-genes,although downregulation of glyco-genes was not always followed by an unambiguous change in the corresponding glycan structures.The effect is better seen as an overall change in the total HepG2 N-glycome,primarily due to the extension of biantennary glycans.We propose an alternative way to evaluate the N-glycome composition via estimating the overall complexity of the glycome by quantifying the number of monomers in each glycan structure.We also propose a model showing feedback loops with the mutual activation of HNF1A-FOXA2 and HNF4A-FOXA2 affecting glyco-genes and protein glycosylation in HepG2 cells.
文摘BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental condition characterized by heterogeneous symptoms and genetic underpinnings.Recent advancements in genetic and epigenetic research have provided insights into the intricate mechanisms contributing to ASD,influencing both diagnosis and therapeutic strategies.AIM To explore the genetic architecture of ASD,elucidate mechanistic insights into genetic mutations,and examine gene-environment interactions.METHODS A comprehensive systematic review was conducted,integrating findings from studies on genetic variations,epigenetic mechanisms(such as DNA methylation and histone modifications),and emerging technologies[including Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)-Cas9 and single-cell RNA sequencing].Relevant articles were identified through systematic searches of databases such as PubMed and Google Scholar.RESULTS Genetic studies have identified numerous risk genes and mutations associated with ASD,yet many cases remain unexplained by known factors,suggesting undiscovered genetic components.Mechanistic insights into how these genetic mutations impact neural development and brain connectivity are still evolving.Epigenetic modifications,particularly DNA methylation and non-coding RNAs,also play significant roles in ASD pathogenesis.Emerging technologies like CRISPR-Cas9 and advanced bioinformatics are advancing our understanding by enabling precise genetic editing and analysis of complex genomic data.CONCLUSION Continued research into the genetic and epigenetic underpinnings of ASD is crucial for developing personalized and effective treatments.Collaborative efforts integrating multidisciplinary expertise and international collaborations are essential to address the complexity of ASD and translate genetic discoveries into clinical practice.Addressing unresolved questions and ethical considerations surrounding genetic research will pave the way for improved diagnostic tools and targeted therapies,ultimately enhancing outcomes for individuals affected by ASD.
