Title |
In utero nanoparticle delivery for site-specific genome editing
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Published in |
Nature Communications, June 2018
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DOI | 10.1038/s41467-018-04894-2 |
Pubmed ID | |
Authors |
Adele S. Ricciardi, Raman Bahal, James S. Farrelly, Elias Quijano, Anthony H. Bianchi, Valerie L. Luks, Rachael Putman, Francesc López-Giráldez, Süleyman Coşkun, Eric Song, Yanfeng Liu, Wei-Che Hsieh, Danith H. Ly, David H. Stitelman, Peter M. Glazer, W. Mark Saltzman |
Abstract |
Genetic diseases can be diagnosed early during pregnancy, but many monogenic disorders continue to cause considerable neonatal and pediatric morbidity and mortality. Early intervention through intrauterine gene editing, however, could correct the genetic defect, potentially allowing for normal organ development, functional disease improvement, or cure. Here we demonstrate safe intravenous and intra-amniotic administration of polymeric nanoparticles to fetal mouse tissues at selected gestational ages with no effect on survival or postnatal growth. In utero introduction of nanoparticles containing peptide nucleic acids (PNAs) and donor DNAs corrects a disease-causing mutation in the β-globin gene in a mouse model of human β-thalassemia, yielding sustained postnatal elevation of blood hemoglobin levels into the normal range, reduced reticulocyte counts, reversal of splenomegaly, and improved survival, with no detected off-target mutations in partially homologous loci. This work may provide the basis for a safe and versatile method of fetal gene editing for human monogenic disorders. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 12 | 21% |
Spain | 3 | 5% |
Japan | 2 | 4% |
Australia | 2 | 4% |
France | 2 | 4% |
United Kingdom | 2 | 4% |
Canada | 1 | 2% |
Russia | 1 | 2% |
India | 1 | 2% |
Other | 4 | 7% |
Unknown | 27 | 47% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 35 | 61% |
Scientists | 17 | 30% |
Science communicators (journalists, bloggers, editors) | 4 | 7% |
Practitioners (doctors, other healthcare professionals) | 1 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 167 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 32 | 19% |
Student > Ph. D. Student | 27 | 16% |
Researcher | 23 | 14% |
Student > Master | 17 | 10% |
Student > Doctoral Student | 7 | 4% |
Other | 18 | 11% |
Unknown | 43 | 26% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 41 | 25% |
Medicine and Dentistry | 21 | 13% |
Agricultural and Biological Sciences | 13 | 8% |
Chemistry | 11 | 7% |
Engineering | 8 | 5% |
Other | 23 | 14% |
Unknown | 50 | 30% |