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State University Spokane
Using modified foamy retroviral vectors to deliver gene therapy may reduce the risk of genotoxicity, according to research published in Scientific Reports.
These vectors have demonstrated promise in vitro, and researchers believe they could be used to treat X-linked severe combined immunodeficiency, thalassemia, and other diseases.
“We’ve started to translate this in collaboration with other scientists and medical doctors into the clinic,” said study author Grant Trobridge, PhD, of Washington State University Spokane.
Dr Trobridge and his colleagues said they decided to pursue foamy retroviral vectors as a delivery system for gene therapy because these vectors are less likely than gammaretroviral vectors or lentiviral vectors to activate nearby genes, including proto-oncogenes.
Still, the researchers altered the foamy retroviral vectors to change how they interact with target stem cells in an attempt to ensure the vectors would insert themselves into safer parts of the genome.
The team said they were able to retarget the foamy retroviral vectors away from genes and into satellite regions enriched for trimethylated histone H3 at lysine 9 by modifying the foamy virus Gag and Pol proteins.
These retargeted foamy retroviral vectors integrated near genes significantly less often than unmodified foamy retroviral vectors (P<0.001).
The researchers also noted that their retargeted foamy retroviral vectors can be produced at clinically relevant titers, and engineered target cells are not needed. Any target cell can be used by using alternate foamy helper plasmids during vector production. 
Photo courtesy of Washington
State University Spokane
Using modified foamy retroviral vectors to deliver gene therapy may reduce the risk of genotoxicity, according to research published in Scientific Reports.
These vectors have demonstrated promise in vitro, and researchers believe they could be used to treat X-linked severe combined immunodeficiency, thalassemia, and other diseases.
“We’ve started to translate this in collaboration with other scientists and medical doctors into the clinic,” said study author Grant Trobridge, PhD, of Washington State University Spokane.
Dr Trobridge and his colleagues said they decided to pursue foamy retroviral vectors as a delivery system for gene therapy because these vectors are less likely than gammaretroviral vectors or lentiviral vectors to activate nearby genes, including proto-oncogenes.
Still, the researchers altered the foamy retroviral vectors to change how they interact with target stem cells in an attempt to ensure the vectors would insert themselves into safer parts of the genome.
The team said they were able to retarget the foamy retroviral vectors away from genes and into satellite regions enriched for trimethylated histone H3 at lysine 9 by modifying the foamy virus Gag and Pol proteins.
These retargeted foamy retroviral vectors integrated near genes significantly less often than unmodified foamy retroviral vectors (P<0.001).
The researchers also noted that their retargeted foamy retroviral vectors can be produced at clinically relevant titers, and engineered target cells are not needed. Any target cell can be used by using alternate foamy helper plasmids during vector production.
Photo courtesy of Washington
State University Spokane
Using modified foamy retroviral vectors to deliver gene therapy may reduce the risk of genotoxicity, according to research published in Scientific Reports.
These vectors have demonstrated promise in vitro, and researchers believe they could be used to treat X-linked severe combined immunodeficiency, thalassemia, and other diseases.
“We’ve started to translate this in collaboration with other scientists and medical doctors into the clinic,” said study author Grant Trobridge, PhD, of Washington State University Spokane.
Dr Trobridge and his colleagues said they decided to pursue foamy retroviral vectors as a delivery system for gene therapy because these vectors are less likely than gammaretroviral vectors or lentiviral vectors to activate nearby genes, including proto-oncogenes.
Still, the researchers altered the foamy retroviral vectors to change how they interact with target stem cells in an attempt to ensure the vectors would insert themselves into safer parts of the genome.
The team said they were able to retarget the foamy retroviral vectors away from genes and into satellite regions enriched for trimethylated histone H3 at lysine 9 by modifying the foamy virus Gag and Pol proteins.
These retargeted foamy retroviral vectors integrated near genes significantly less often than unmodified foamy retroviral vectors (P<0.001).
The researchers also noted that their retargeted foamy retroviral vectors can be produced at clinically relevant titers, and engineered target cells are not needed. Any target cell can be used by using alternate foamy helper plasmids during vector production.