<p class="title">Scientists using gene editing tool CRISPR/Cas9 have identified the cause and potential treatment of a fatal respiratory disorder in newborn infants that turns their lips and skin blue.</p>.<p class="bodytext">The team used CRISPR/Cas9 to generate mice that mimic the mostly untreatable disorder called Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV).</p>.<p class="bodytext">The model allowed researchers from Cincinnati Children's Hospital in the US to pinpoint the ailment's cause and develop a potential and desperately needed nanoparticle-based treatment.</p>.<p class="bodytext">ACDMPV usually strikes infants within a month of birth. The disease starves the pulmonary system of oxygen after the lung's blood vessels do not form properly during organ development.</p>.<p class="bodytext">The lack of tiny blood vessels called alveolar capillaries causes hypoxia, inflammation, and death, researchers said.</p>.<p class="bodytext">"There are no effective treatments other than a lung transplant, so the need for new therapeutics is urgent," said Vlad Kalinichenko, at the Cincinnati Children's.</p>.<p class="bodytext">"We identified a nanoparticle therapeutic strategy to increase the number of alveolar capillaries and help preserve respiratory function for at least a subset of the babies with this congenital lung disease," said Kalinichenko, lead study investigator in the study published in the journal American Journal of Respiratory and Critical Care Medicine.</p>.<p class="bodytext">The disease has long been linked to mutations in the FOXF1 gene, an important regulator of embryonic lung development.</p>.<p class="bodytext">The remaining mystery until this study is precise microbiological processes that fuel ACDMPV, researchers said.</p>.<p class="bodytext">Researchers analysed genetic information from human ACDMPV cases to generate the first clinically relevant animal model of ACDMPV. They used CRISPR/Cas9 to recreate human FOXF1 mutations in the mouse.</p>.<p class="bodytext">CRISPR-Cas9 allows precise gene editing by using an enzyme to cut out specific sections of a DNA sequence and reattaching the loose ends at the desired point to change a cell's genetic makeup.</p>.<p class="bodytext">Having clinically accurate mouse models of disease ACDMPV allowed the scientists to overcome a longtime hurdle to understanding how the disease develops, researchers said.</p>.<p class="bodytext">By studying protein-DNA interactions linked to the FOXF1 gene in pulmonary cells, researchers found a specific point mutation, which blocked molecular signalling to multiple downstream target genes involved in the formation of pulmonary blood vessels.</p>.<p class="bodytext">The researchers theorised that treating newborn mice with a protein called STAT3 would stimulate blood vessel development in the lungs.</p>.<p class="bodytext">Researchers turned to nanoparticle technology to deliver a STAT3 mini-gene to lungs of newborn mice. They created a novel formulation for what are known as polyethyleneimine (PEI) nanoparticles.</p>.<p class="bodytext">The gelatin-like PEI nanoparticles can carry therapeutic genetic material to different parts of the body by administering them to patients intravenously.</p>.<p class="bodytext">Different formulations of PEI nanoparticles are currently being tested in clinical trials for adult cancer at other institutions, researchers said. </p>
<p class="title">Scientists using gene editing tool CRISPR/Cas9 have identified the cause and potential treatment of a fatal respiratory disorder in newborn infants that turns their lips and skin blue.</p>.<p class="bodytext">The team used CRISPR/Cas9 to generate mice that mimic the mostly untreatable disorder called Alveolar Capillary Dysplasia with Misalignment of Pulmonary Veins (ACDMPV).</p>.<p class="bodytext">The model allowed researchers from Cincinnati Children's Hospital in the US to pinpoint the ailment's cause and develop a potential and desperately needed nanoparticle-based treatment.</p>.<p class="bodytext">ACDMPV usually strikes infants within a month of birth. The disease starves the pulmonary system of oxygen after the lung's blood vessels do not form properly during organ development.</p>.<p class="bodytext">The lack of tiny blood vessels called alveolar capillaries causes hypoxia, inflammation, and death, researchers said.</p>.<p class="bodytext">"There are no effective treatments other than a lung transplant, so the need for new therapeutics is urgent," said Vlad Kalinichenko, at the Cincinnati Children's.</p>.<p class="bodytext">"We identified a nanoparticle therapeutic strategy to increase the number of alveolar capillaries and help preserve respiratory function for at least a subset of the babies with this congenital lung disease," said Kalinichenko, lead study investigator in the study published in the journal American Journal of Respiratory and Critical Care Medicine.</p>.<p class="bodytext">The disease has long been linked to mutations in the FOXF1 gene, an important regulator of embryonic lung development.</p>.<p class="bodytext">The remaining mystery until this study is precise microbiological processes that fuel ACDMPV, researchers said.</p>.<p class="bodytext">Researchers analysed genetic information from human ACDMPV cases to generate the first clinically relevant animal model of ACDMPV. They used CRISPR/Cas9 to recreate human FOXF1 mutations in the mouse.</p>.<p class="bodytext">CRISPR-Cas9 allows precise gene editing by using an enzyme to cut out specific sections of a DNA sequence and reattaching the loose ends at the desired point to change a cell's genetic makeup.</p>.<p class="bodytext">Having clinically accurate mouse models of disease ACDMPV allowed the scientists to overcome a longtime hurdle to understanding how the disease develops, researchers said.</p>.<p class="bodytext">By studying protein-DNA interactions linked to the FOXF1 gene in pulmonary cells, researchers found a specific point mutation, which blocked molecular signalling to multiple downstream target genes involved in the formation of pulmonary blood vessels.</p>.<p class="bodytext">The researchers theorised that treating newborn mice with a protein called STAT3 would stimulate blood vessel development in the lungs.</p>.<p class="bodytext">Researchers turned to nanoparticle technology to deliver a STAT3 mini-gene to lungs of newborn mice. They created a novel formulation for what are known as polyethyleneimine (PEI) nanoparticles.</p>.<p class="bodytext">The gelatin-like PEI nanoparticles can carry therapeutic genetic material to different parts of the body by administering them to patients intravenously.</p>.<p class="bodytext">Different formulations of PEI nanoparticles are currently being tested in clinical trials for adult cancer at other institutions, researchers said. </p>