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posted by janrinok on Tuesday June 26 2018, @07:58PM   Printer-friendly
from the today's-word-is-'splenomegaly' dept.

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.

[...] Unlike gene editing technologies that rely on the activity of exogenously delivered nucleases18,19—such as zinc finger nucleases, TAL effector nucleases, and CRISPR/Cas9—PNA/DNA NPs can be readily administered in vivo and have been shown to have extremely low to undetectable off-target effects in the genome because the PNA editing molecules lack inherent nuclease activity5,6,7.

[...] Unlike other gene editing technologies that rely on activity of exogenous nucleases (CRISPR/Cas, TAL effector nucleases and zinc finger nucleases) that can create extraneous double-stranded breaks, PNA-mediated gene editing makes use of endogenous, high fidelity repair pathways, which reduces the risk of error-prone end-joining causing additional mutations. With continuing concern regarding off-target effects of CRISPR/Cas951 and the finding that Cas9 proteins can illicit an adaptive immune response52, the safety profile of PNA/DNA editing may be particularly attractive, as avoiding off-target mutations is of exceptional importance during fetal development.

https://www.nature.com/articles/s41467-018-04894-2


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  • (Score: 2) by takyon on Tuesday June 26 2018, @09:00PM (1 child)

    by takyon (881) <reversethis-{gro ... s} {ta} {noykat}> on Tuesday June 26 2018, @09:00PM (#698964) Journal

    Somebody will figure out each piece of the puzzle eventually, and it will spread around.

    --
    [SIG] 10/28/2017: Soylent Upgrade v14 [soylentnews.org]
    Starting Score:    1  point
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  • (Score: 0) by Anonymous Coward on Tuesday June 26 2018, @09:22PM

    by Anonymous Coward on Tuesday June 26 2018, @09:22PM (#698973)

    The OP is not a new idea [wikipedia.org]:

    Nucleic acid triplexes were first observed experimental 60years ago by Rich and coworkers upon mixing the polyribonucleotides polyU and polyA in a 2:1 ratio (27). Frank-Kamenetskii’s group later showed that a homopurine-homopyrimidine mirror repeat within a supercoiled plasmid was capable of forming an intramolecular triplex under low pH conditions (28,29), implicating a physiological role for these complexes in gene regulation, as well as the cause of genome instability (30). Around this time, the Dervan and Helene laboratories realised that the formation of an intermolecular triplex by a synthetic oligonucleotide (31,32) could provide a means to target unique genomic sequences and allow the modulation of specific genes (33). However, since these seminal studies there has been limited evidence for the formation of triplexes within genomic DNA, and interest in their use for gene-targeting has dwindled, perhaps due to the growing success of other gene-targeting methodologies, such as zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs). Nevertheless, this work serendipitously laid the foundation for the application of triplexes to DNA nanotechnology.

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814803/ [nih.gov]

    I'd guess its more that old ideas (primarily from the pre-1940 era) will be picked back up and the "NHST era" will be left to history.