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Research paper thumbnail of Intentional or inadvertent fake news sharing? Fact-checking warnings and users’ interaction with social media content

El profesional de la información, 2020

The main social media platforms have been implementing strategies to minimize fake news dissemina... more The main social media platforms have been implementing strategies to minimize fake news dissemination. These include identifying, labeling, and penalizing –via news feed ranking algorithms– fake publications. Part of the rationale behind this approach is that the negative effects of fake content arise only when social media users are deceived. Once debunked, fake posts and news stories should therefore become harmless. Unfortunately, the literature shows that the effects of misinformation are more complex and tend to persist and even backfire after correction. Furthermore, we still do not know much about how social media users evaluate content that has been fact-checked and flagged as false. More worryingly, previous findings suggest that some people may intentionally share made up news on social media, although their motivations are not fully explained. To better understand users’ interaction with social media content identified or recognized as false, we analyze qualitative and qu...

Research paper thumbnail of In vivo analyses of viral RNA translation

Methods in molecular biology (Clifton, N.J.), 2008

Positive-strand RNA viruses often use noncanonical strategies to usurp the host translational mac... more Positive-strand RNA viruses often use noncanonical strategies to usurp the host translational machinery for their own benefit. These strategies have been analyzed using transient expression assays in the absence of replication, with reporter genes replacing viral genes. A sensitive and convenient reporter assay is the dual luciferase system using Renilla (Renilla reniformis) and firefly (Photinus pyralis) reporter genes. Use of recombinant viral constructs containing the reporter luciferase gene allows us to discern whether a particular RNA sequence or secondary structure elicits an effect on initiation of translation or recoding. This chapter describes a standard luciferase protocol that can be molded to fit any viral sequence, in order to detect cis-acting regulatory elements in viral RNA.

Research paper thumbnail of Gene Therapy (517 articles)

BVL-1−like VL30 promoter sustains long-term expression in erythroid progenitor cells , 2002

doi:10.1182/blood-2002-07-2105 BVL-1−like VL30 promoter sustains long-term expression in erythroi... more doi:10.1182/blood-2002-07-2105 BVL-1−like VL30 promoter sustains long-term expression in erythroid progenitor cells Updated information and services can be found at:

Research paper thumbnail of Assessment of Vl30 Erythropoietin Responsive Promoters for Erthyroid Gene Therapy

Congenital blood disorders such as hemoglobinopathies and thalassemias are common, and yet clinic... more Congenital blood disorders such as hemoglobinopathies and thalassemias are common, and yet clinically challenging glob in disorders. Gene therapy was thought to serve as a therapeutic method to treat these disorders through the introduction and expression of a transgenic globin gene. While tremendous advances have been made in vivo, allowing for sickle cell correction in mouse models, gene delivery protocols and vector prototypes still require modification. Vectors have yet to deliver the appropriate level of expression necessary for complete sickle cell amelioration. Alternative gene delivery vector systems derived from VL30 retroelements have been designed in the case of this study, and have proven to be effective in expressing a tissue- specific transgene expression, in vitro. Activation of the erythropoietin (epo)-induced VL30 elements was monitored in two mouse erythroid progenitor cell lines, MEL 585S and ELM-1-1. Reverse transcription of a variety of VL30 epo-responsive promo...

Research paper thumbnail of Momlv-Based Pseudovirion Packaging Cell Line

Research paper thumbnail of Noncoding RNAs of Plant Viruses and Viroids: Sponges of Host Translation and RNA Interference Machinery

Molecular plant-microbe interactions : MPMI, Jan 22, 2016

Noncoding sequences in plant viral genomes are well-known to control viral replication and gene e... more Noncoding sequences in plant viral genomes are well-known to control viral replication and gene expression in cis. However, plant viral and viroid noncoding (nc)RNA sequences can also regulate gene expression acting in trans, often acting like 'sponges' that bind and sequester host cellular machinery to favor viral infection. Noncoding sequences of small subgenomic (sg)RNAs of Barley yellow dwarf virus (BYDV) and Red clover necrotic mosaic virus (RCNMV) contain a cap-independent translation element that binds translation initiation factor eIF4G. We provide new evidence that a sgRNA of BYDV can globally attenuate host translation, probably by sponging eIF4G. Subgenomic ncRNA of RCNMV is generated via 5' to 3' degradation by a host exonuclease. The similar noncoding subgenomic flavivirus (sf)RNA, inhibits the innate immune response, enhancing viral pathogenesis. Cauliflower mosaic virus transcribes massive amounts of a 600-nt ncRNA, which is processed into small RNAs t...

Research paper thumbnail of BVL1-like VL30 promoter sustains long-term expression in erythroid progenitor cells

Blood, 2003

Congenital blood disorders are common and yet clinically challenging globin disorders. Gene thera... more Congenital blood disorders are common and yet clinically challenging globin disorders. Gene therapy continues to serve as a potential therapeutic method to treat these disorders. While tremendous advances have been made in vivo, gene delivery protocols and vector prototypes still require optimization. Alternative cisacting promoter elements derived from VL30 retroelements have been effective in expressing tissue-specific transgene expression in vivo in nonerythroid cells. VL30 promoter elements were isolated from ELM-I-1 erythroid progenitor cells upon erythropoietin (epo) treatment. These promoters were inserted into a VL30-derived expression vector and reintroduced into the ELM-I-1 cells. ␤-Galactosidase reporter gene activity from the ELM 5 clone, a BVL-1-like VL30 promoter, was capable of expressing sustained levels of the transgene expression over a 16-week assay period. These findings delineate the potential utility of these retroelement promoters as transcriptionally active, erythroid-specific, long terminal repeat (LTR) components for current globin vector constructs.

Research paper thumbnail of BVL1-like VL30 promoter sustains long-term expression in erythroid progenitor cells

Research paper thumbnail of Conserved, Erythropoietin-Responsive VL30 Promoters Isolated from Erythroid Progenitor Cells

Blood Cells Molecules and Diseases, 2002

Research paper thumbnail of A replication-incompetent Rift Valley fever vaccine: Chimeric virus-like particles protect mice and rats against lethal challenge

Virology, 2010

Virus-like particles (VLPs) present viral antigens in a native conformation and are effectively r... more Virus-like particles (VLPs) present viral antigens in a native conformation and are effectively recognized by the immune system and therefore are considered as suitable and safe vaccine candidates against many viral diseases.

Research paper thumbnail of The αGal HyperAcute ® Technology: Enhancing Immunogenicity of Antiviral Vaccines by Exploiting the Natural αGal-Mediated Zoonotic Blockade

Zoonoses and Public Health, 2009

The αGal HyperAcute® Technology exploits a robust zoonotic blockade to enhance potency of antivir... more The αGal HyperAcute® Technology exploits a robust zoonotic blockade to enhance potency of antiviral vaccines. Naturally acquired immunity against the common αGal epitope [galactose-alpha(1,3)-galactose-beta(1,4)N-acetylglucosamine-R (Gal-α(1,3)-Gal-β(1,4)-GlcNAc-R)] is facilitated by the loss of a key enzyme in the epitope’s biosynthetic pathway. As human cells are devoid of this epitope, chronic stimulus from gut flora leads to high levels of circulating anti-αGal antibodies and the development of a robust immune pathway. As the αGal epitope is immediately recognized as foreign, the naturally acquired αGal immune pathway in humans serves as a strong barrier to zoonotic infection. The αGal HyperAcute® Technology takes advantage of this natural process to facilitate the rapid presentation of modified antigens to antigen-presenting cells, leading to a strong immune response. The evolutionary immunity to αGal ensures that the presence of αGal epitopes on antigens will lead to a robust immune response involving cross-activation of TH1 immunity, characterized by cytokine secretion and increased phagocytic activity, and TH2 immunity characterized by high antibody titres. αGal epitopes can be applied to antiviral vaccines by biological, enzymatic or chemical means. Several detection methods that directly and indirectly verify αGal addition are discussed. Enhanced immunogenicity (humoral and cellular) of αGal-modified vaccines is shown for several antiviral vaccine candidates. αGal modification of antiviral vaccine components leads to enhanced immunogenicity. The existing body of literature describing the utility of αGal epitopes as a safe and robust immunostimulatory and -modulatory agent in humans supports the basis for applying the αGal HyperAcute® Technology to the improvement of antiviral vaccines, both new and currently approved.

Research paper thumbnail of Rho GTPases Modulate Entry of Ebola Virus and Vesicular Stomatitis Virus Pseudotyped Vectors

Journal of Virology, 2009

To explore mechanisms of entry for Ebola virus (EBOV) glycoprotein (GP) pseudotyped virions, we u... more To explore mechanisms of entry for Ebola virus (EBOV) glycoprotein (GP) pseudotyped virions, we used comparative gene analysis to identify genes whose expression correlated with viral transduction. Candidate genes were identified by using EBOV GP pseudotyped virions to transduce human tumor cell lines that had previously been characterized by cDNA microarray. Transduction profiles for each of these cell lines were generated, and a significant positive correlation was observed between RhoC expression and permissivity for EBOV vector transduction. This correlation was not specific for EBOV vector alone as RhoC also correlated highly with transduction of vesicular stomatitis virus GP (VSVG) pseudotyped vector. Levels of RhoC protein in EBOV and VSV permissive and nonpermissive cells were consistent with the cDNA gene array findings.

Research paper thumbnail of Rho GTPases Modulate Entry of Ebola Virus and Vesicular Stomatitis Virus Pseudotyped Vectors

To explore mechanisms of entry for Ebola virus (EBOV) glycoprotein (GP) pseudotyped virions, we u... more To explore mechanisms of entry for Ebola virus (EBOV) glycoprotein (GP) pseudotyped virions, we used comparative gene analysis to identify genes whose expression correlated with viral transduction. Candidate genes were identified by using EBOV GP pseudotyped virions to transduce human tumor cell lines that had previously been characterized by cDNA microarray. Transduction profiles for each of these cell lines were generated, and a significant positive correlation was observed between RhoC expression and permissivity for EBOV vector transduction. This correlation was not specific for EBOV vector alone as RhoC also correlated highly with transduction of vesicular stomatitis virus GP (VSVG) pseudotyped vector. Levels of RhoC protein in EBOV and VSV permissive and nonpermissive cells were consistent with the cDNA gene array findings.

Research paper thumbnail of In Vivo Analyses of Viral RNA Translation

Positive-strand RNA viruses often use noncanonical strategies to usurp the host translational mac... more Positive-strand RNA viruses often use noncanonical strategies to usurp the host translational machinery for their own benefit. These strategies have been analyzed using transient expression assays in the absence of replication, with reporter genes replacing viral genes. A sensitive and convenient reporter assay is the dual luciferase system using Renilla (Renilla reniformis) and firefly (Photinus pyralis) reporter genes. Use of recombinant viral constructs containing the reporter luciferase gene allows us to discern whether a particular RNA sequence or secondary structure elicits an effect on initiation of translation or recoding. This chapter describes a standard luciferase protocol that can be molded to fit any viral sequence, in order to detect cis-acting regulatory elements in viral RNA.

Research paper thumbnail of A replication-incompetent Rift Valley fever vaccine: Chimeric virus-like particles protect mice and rats against lethal challenge

Virus-like particles (VLPs) present viral antigens in a native conformation and are effectively r... more Virus-like particles (VLPs) present viral antigens in a native conformation and are effectively recognized by the immune system and therefore are considered as suitable and safe vaccine candidates against many viral diseases. Here we demonstrate that chimeric VLPs containing Rift Valley fever virus (RVFV) glycoproteins G N and G C , nucleoprotein N and the gag protein of Moloney murine leukemia virus represent an effective vaccine candidate against Rift Valley fever, a deadly disease in humans and livestock. Long-lasting humoral and cellular immune responses are demonstrated in a mouse model by the analysis of neutralizing antibody titers and cytokine secretion profiles. Vaccine efficacy studies were performed in mouse and rat lethal challenge models resulting in high protection rates. Taken together, these results demonstrate that replication-incompetent chimeric RVF VLPs are an efficient RVFV vaccine candidate.

Research paper thumbnail of BVL-1–like VL30 promoter sustains long-term expression in erythroid progenitor cells

Congenital blood disorders are common and yet clinically challenging globin disorders. Gene thera... more Congenital blood disorders are common and yet clinically challenging globin disorders. Gene therapy continues to serve as a potential therapeutic method to treat these disorders. While tremendous advances have been made in vivo, gene delivery protocols and vector prototypes still require optimization. Alternative cisacting promoter elements derived from VL30 retroelements have been effective in expressing tissue-specific transgene expression in vivo in nonerythroid cells. VL30 promoter elements were isolated from ELM-I-1 erythroid progenitor cells upon erythropoietin (epo) treatment. These promoters were inserted into a VL30-derived expression vector and reintroduced into the ELM-I-1 cells. ␤-Galactosidase reporter gene activity from the ELM 5 clone, a BVL-1-like VL30 promoter, was capable of expressing sustained levels of the transgene expression over a 16-week assay period. These findings delineate the potential utility of these retroelement promoters as transcriptionally active, erythroid-specific, long terminal repeat (LTR) components for current globin vector constructs.

Research paper thumbnail of Intentional or inadvertent fake news sharing? Fact-checking warnings and users’ interaction with social media content

El profesional de la información, 2020

The main social media platforms have been implementing strategies to minimize fake news dissemina... more The main social media platforms have been implementing strategies to minimize fake news dissemination. These include identifying, labeling, and penalizing –via news feed ranking algorithms– fake publications. Part of the rationale behind this approach is that the negative effects of fake content arise only when social media users are deceived. Once debunked, fake posts and news stories should therefore become harmless. Unfortunately, the literature shows that the effects of misinformation are more complex and tend to persist and even backfire after correction. Furthermore, we still do not know much about how social media users evaluate content that has been fact-checked and flagged as false. More worryingly, previous findings suggest that some people may intentionally share made up news on social media, although their motivations are not fully explained. To better understand users’ interaction with social media content identified or recognized as false, we analyze qualitative and qu...

Research paper thumbnail of In vivo analyses of viral RNA translation

Methods in molecular biology (Clifton, N.J.), 2008

Positive-strand RNA viruses often use noncanonical strategies to usurp the host translational mac... more Positive-strand RNA viruses often use noncanonical strategies to usurp the host translational machinery for their own benefit. These strategies have been analyzed using transient expression assays in the absence of replication, with reporter genes replacing viral genes. A sensitive and convenient reporter assay is the dual luciferase system using Renilla (Renilla reniformis) and firefly (Photinus pyralis) reporter genes. Use of recombinant viral constructs containing the reporter luciferase gene allows us to discern whether a particular RNA sequence or secondary structure elicits an effect on initiation of translation or recoding. This chapter describes a standard luciferase protocol that can be molded to fit any viral sequence, in order to detect cis-acting regulatory elements in viral RNA.

Research paper thumbnail of Gene Therapy (517 articles)

BVL-1−like VL30 promoter sustains long-term expression in erythroid progenitor cells , 2002

doi:10.1182/blood-2002-07-2105 BVL-1−like VL30 promoter sustains long-term expression in erythroi... more doi:10.1182/blood-2002-07-2105 BVL-1−like VL30 promoter sustains long-term expression in erythroid progenitor cells Updated information and services can be found at:

Research paper thumbnail of Assessment of Vl30 Erythropoietin Responsive Promoters for Erthyroid Gene Therapy

Congenital blood disorders such as hemoglobinopathies and thalassemias are common, and yet clinic... more Congenital blood disorders such as hemoglobinopathies and thalassemias are common, and yet clinically challenging glob in disorders. Gene therapy was thought to serve as a therapeutic method to treat these disorders through the introduction and expression of a transgenic globin gene. While tremendous advances have been made in vivo, allowing for sickle cell correction in mouse models, gene delivery protocols and vector prototypes still require modification. Vectors have yet to deliver the appropriate level of expression necessary for complete sickle cell amelioration. Alternative gene delivery vector systems derived from VL30 retroelements have been designed in the case of this study, and have proven to be effective in expressing a tissue- specific transgene expression, in vitro. Activation of the erythropoietin (epo)-induced VL30 elements was monitored in two mouse erythroid progenitor cell lines, MEL 585S and ELM-1-1. Reverse transcription of a variety of VL30 epo-responsive promo...

Research paper thumbnail of Momlv-Based Pseudovirion Packaging Cell Line

Research paper thumbnail of Noncoding RNAs of Plant Viruses and Viroids: Sponges of Host Translation and RNA Interference Machinery

Molecular plant-microbe interactions : MPMI, Jan 22, 2016

Noncoding sequences in plant viral genomes are well-known to control viral replication and gene e... more Noncoding sequences in plant viral genomes are well-known to control viral replication and gene expression in cis. However, plant viral and viroid noncoding (nc)RNA sequences can also regulate gene expression acting in trans, often acting like 'sponges' that bind and sequester host cellular machinery to favor viral infection. Noncoding sequences of small subgenomic (sg)RNAs of Barley yellow dwarf virus (BYDV) and Red clover necrotic mosaic virus (RCNMV) contain a cap-independent translation element that binds translation initiation factor eIF4G. We provide new evidence that a sgRNA of BYDV can globally attenuate host translation, probably by sponging eIF4G. Subgenomic ncRNA of RCNMV is generated via 5' to 3' degradation by a host exonuclease. The similar noncoding subgenomic flavivirus (sf)RNA, inhibits the innate immune response, enhancing viral pathogenesis. Cauliflower mosaic virus transcribes massive amounts of a 600-nt ncRNA, which is processed into small RNAs t...

Research paper thumbnail of BVL1-like VL30 promoter sustains long-term expression in erythroid progenitor cells

Blood, 2003

Congenital blood disorders are common and yet clinically challenging globin disorders. Gene thera... more Congenital blood disorders are common and yet clinically challenging globin disorders. Gene therapy continues to serve as a potential therapeutic method to treat these disorders. While tremendous advances have been made in vivo, gene delivery protocols and vector prototypes still require optimization. Alternative cisacting promoter elements derived from VL30 retroelements have been effective in expressing tissue-specific transgene expression in vivo in nonerythroid cells. VL30 promoter elements were isolated from ELM-I-1 erythroid progenitor cells upon erythropoietin (epo) treatment. These promoters were inserted into a VL30-derived expression vector and reintroduced into the ELM-I-1 cells. ␤-Galactosidase reporter gene activity from the ELM 5 clone, a BVL-1-like VL30 promoter, was capable of expressing sustained levels of the transgene expression over a 16-week assay period. These findings delineate the potential utility of these retroelement promoters as transcriptionally active, erythroid-specific, long terminal repeat (LTR) components for current globin vector constructs.

Research paper thumbnail of BVL1-like VL30 promoter sustains long-term expression in erythroid progenitor cells

Research paper thumbnail of Conserved, Erythropoietin-Responsive VL30 Promoters Isolated from Erythroid Progenitor Cells

Blood Cells Molecules and Diseases, 2002

Research paper thumbnail of A replication-incompetent Rift Valley fever vaccine: Chimeric virus-like particles protect mice and rats against lethal challenge

Virology, 2010

Virus-like particles (VLPs) present viral antigens in a native conformation and are effectively r... more Virus-like particles (VLPs) present viral antigens in a native conformation and are effectively recognized by the immune system and therefore are considered as suitable and safe vaccine candidates against many viral diseases.

Research paper thumbnail of The αGal HyperAcute ® Technology: Enhancing Immunogenicity of Antiviral Vaccines by Exploiting the Natural αGal-Mediated Zoonotic Blockade

Zoonoses and Public Health, 2009

The αGal HyperAcute® Technology exploits a robust zoonotic blockade to enhance potency of antivir... more The αGal HyperAcute® Technology exploits a robust zoonotic blockade to enhance potency of antiviral vaccines. Naturally acquired immunity against the common αGal epitope [galactose-alpha(1,3)-galactose-beta(1,4)N-acetylglucosamine-R (Gal-α(1,3)-Gal-β(1,4)-GlcNAc-R)] is facilitated by the loss of a key enzyme in the epitope’s biosynthetic pathway. As human cells are devoid of this epitope, chronic stimulus from gut flora leads to high levels of circulating anti-αGal antibodies and the development of a robust immune pathway. As the αGal epitope is immediately recognized as foreign, the naturally acquired αGal immune pathway in humans serves as a strong barrier to zoonotic infection. The αGal HyperAcute® Technology takes advantage of this natural process to facilitate the rapid presentation of modified antigens to antigen-presenting cells, leading to a strong immune response. The evolutionary immunity to αGal ensures that the presence of αGal epitopes on antigens will lead to a robust immune response involving cross-activation of TH1 immunity, characterized by cytokine secretion and increased phagocytic activity, and TH2 immunity characterized by high antibody titres. αGal epitopes can be applied to antiviral vaccines by biological, enzymatic or chemical means. Several detection methods that directly and indirectly verify αGal addition are discussed. Enhanced immunogenicity (humoral and cellular) of αGal-modified vaccines is shown for several antiviral vaccine candidates. αGal modification of antiviral vaccine components leads to enhanced immunogenicity. The existing body of literature describing the utility of αGal epitopes as a safe and robust immunostimulatory and -modulatory agent in humans supports the basis for applying the αGal HyperAcute® Technology to the improvement of antiviral vaccines, both new and currently approved.

Research paper thumbnail of Rho GTPases Modulate Entry of Ebola Virus and Vesicular Stomatitis Virus Pseudotyped Vectors

Journal of Virology, 2009

To explore mechanisms of entry for Ebola virus (EBOV) glycoprotein (GP) pseudotyped virions, we u... more To explore mechanisms of entry for Ebola virus (EBOV) glycoprotein (GP) pseudotyped virions, we used comparative gene analysis to identify genes whose expression correlated with viral transduction. Candidate genes were identified by using EBOV GP pseudotyped virions to transduce human tumor cell lines that had previously been characterized by cDNA microarray. Transduction profiles for each of these cell lines were generated, and a significant positive correlation was observed between RhoC expression and permissivity for EBOV vector transduction. This correlation was not specific for EBOV vector alone as RhoC also correlated highly with transduction of vesicular stomatitis virus GP (VSVG) pseudotyped vector. Levels of RhoC protein in EBOV and VSV permissive and nonpermissive cells were consistent with the cDNA gene array findings.

Research paper thumbnail of Rho GTPases Modulate Entry of Ebola Virus and Vesicular Stomatitis Virus Pseudotyped Vectors

To explore mechanisms of entry for Ebola virus (EBOV) glycoprotein (GP) pseudotyped virions, we u... more To explore mechanisms of entry for Ebola virus (EBOV) glycoprotein (GP) pseudotyped virions, we used comparative gene analysis to identify genes whose expression correlated with viral transduction. Candidate genes were identified by using EBOV GP pseudotyped virions to transduce human tumor cell lines that had previously been characterized by cDNA microarray. Transduction profiles for each of these cell lines were generated, and a significant positive correlation was observed between RhoC expression and permissivity for EBOV vector transduction. This correlation was not specific for EBOV vector alone as RhoC also correlated highly with transduction of vesicular stomatitis virus GP (VSVG) pseudotyped vector. Levels of RhoC protein in EBOV and VSV permissive and nonpermissive cells were consistent with the cDNA gene array findings.

Research paper thumbnail of In Vivo Analyses of Viral RNA Translation

Positive-strand RNA viruses often use noncanonical strategies to usurp the host translational mac... more Positive-strand RNA viruses often use noncanonical strategies to usurp the host translational machinery for their own benefit. These strategies have been analyzed using transient expression assays in the absence of replication, with reporter genes replacing viral genes. A sensitive and convenient reporter assay is the dual luciferase system using Renilla (Renilla reniformis) and firefly (Photinus pyralis) reporter genes. Use of recombinant viral constructs containing the reporter luciferase gene allows us to discern whether a particular RNA sequence or secondary structure elicits an effect on initiation of translation or recoding. This chapter describes a standard luciferase protocol that can be molded to fit any viral sequence, in order to detect cis-acting regulatory elements in viral RNA.

Research paper thumbnail of A replication-incompetent Rift Valley fever vaccine: Chimeric virus-like particles protect mice and rats against lethal challenge

Virus-like particles (VLPs) present viral antigens in a native conformation and are effectively r... more Virus-like particles (VLPs) present viral antigens in a native conformation and are effectively recognized by the immune system and therefore are considered as suitable and safe vaccine candidates against many viral diseases. Here we demonstrate that chimeric VLPs containing Rift Valley fever virus (RVFV) glycoproteins G N and G C , nucleoprotein N and the gag protein of Moloney murine leukemia virus represent an effective vaccine candidate against Rift Valley fever, a deadly disease in humans and livestock. Long-lasting humoral and cellular immune responses are demonstrated in a mouse model by the analysis of neutralizing antibody titers and cytokine secretion profiles. Vaccine efficacy studies were performed in mouse and rat lethal challenge models resulting in high protection rates. Taken together, these results demonstrate that replication-incompetent chimeric RVF VLPs are an efficient RVFV vaccine candidate.

Research paper thumbnail of BVL-1–like VL30 promoter sustains long-term expression in erythroid progenitor cells

Congenital blood disorders are common and yet clinically challenging globin disorders. Gene thera... more Congenital blood disorders are common and yet clinically challenging globin disorders. Gene therapy continues to serve as a potential therapeutic method to treat these disorders. While tremendous advances have been made in vivo, gene delivery protocols and vector prototypes still require optimization. Alternative cisacting promoter elements derived from VL30 retroelements have been effective in expressing tissue-specific transgene expression in vivo in nonerythroid cells. VL30 promoter elements were isolated from ELM-I-1 erythroid progenitor cells upon erythropoietin (epo) treatment. These promoters were inserted into a VL30-derived expression vector and reintroduced into the ELM-I-1 cells. ␤-Galactosidase reporter gene activity from the ELM 5 clone, a BVL-1-like VL30 promoter, was capable of expressing sustained levels of the transgene expression over a 16-week assay period. These findings delineate the potential utility of these retroelement promoters as transcriptionally active, erythroid-specific, long terminal repeat (LTR) components for current globin vector constructs.