The structure of compacted soils is characterised by decreased (macro-)porosity, which leads to increased mechanical impedance and decreased fluid transport rates, resulting in reduced root growth ...and crop productivity. Particularly in soils with high mechanical impedance, macropores can be used by roots as pathways of least resistance. This study investigated how different soil physical states relate to whole plant growth and whether roots grow towards spots with favourable soil physical conditions. Experiments were conducted under controlled and field conditions. Soybean (Glycine max L.), wheat (Triticum aestivum L.) and maize (Zea mays L.) were grown on uncompacted soil, compacted soil and compacted soil with artificial macropores. The interactions between roots and artificial macropores were quantified using X-ray computed tomography. Active growth of roots towards artificial macropores was observed for all three species. Roots grew either into macropores (predominantly in maize) or crossed them (predominantly in wheat). The presence of artificial macropores in compacted soil enabled all three species to compensate for decreased early vigour at later developmental stages. These results show that roots sense their physical environment, enabling them to grow towards spots with favourable soil conditions. The different kinds of root-macropore interaction indicated that macropores serve as a path of least resistance and a source of oxygen, both resulting in increased crop productivity on compacted soils.
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•Artificial macropores restore certain soil physical functions of compacted soils.•Crop roots preferentially grow towards artificial macropores in compacted soil.•Artificial macropores provide different functions for roots in compacted soil.•Artificial macropores increase soil fertility and crop growth in compacted soil.
Skeletal muscle is a target tissue of choice for the gene therapy of both muscle and non-muscle disorders. Investigations of gene transfer into muscle have progressed considerably from the expression ...of plasmid reporter genes to the production of therapeutic proteins such as trophic factors, hormones, antigens, ion channels or cytoskeletal proteins. Viral vectors are intrinsically the most efficient vehicles to deliver genes into skeletal muscles. But, because viruses are associated with a variety of problems (such as immune and inflammatory responses, toxicity, limited large scale production yields, limitations in the size of the carried therapeutic genes), nonviral vectors remain a viable alternative. In addition, as nonviral vectors allow to transfer genetic structures of various sizes (including large plasmid DNA carrying full-length coding sequences of the gene of interest), they can be used in various gene therapy approaches. However, given the lack of efficiency of nonviral vectors in experimental studies and in the clinical settings, the overall outcome clearly indicates that improved synthetic vectors and/or delivery techniques are required for successful clinical gene therapy. Today, most of the potential muscle-targeted clinical applications seem geared toward peripheral ischemia (mainly through local injections) and cancer and infectious vaccines, and one locoregional administration of naked DNA in Duchenne muscular dystrophy. This review updates the developments in clinical applications of the various plasmid-based non-viral methods under investigation for the delivery of genes to muscles.
It is worth stating that a generation is needed to bring about a new family of drugs. After the deciphering of the genetic cause in 1995, two innovative classes of therapeutics are now available for ...spinal muscular atrophy (SMA): the repeated administration of antisens oligonucleotides and the one-shot administration of a scAAV9-SMN as a gene therapy. By addressing the genetic mechanisms of the disease, these drugs fundamentally change its course. These major advances in an extremely severe disease, often fatal before the age of 18 months in the type 1 form (50% of patients), pave the way for the treatment of other serious pathologies of the nervous or neuromuscular system, and provide unambiguous evidence of the effectiveness of these new classes of drugs called to address a number of genetic or acquired diseases. These breakthroughs raise also new scientific and technological questions (limited production yields of gene therapy drugs) but also ethical issues (access of patients to these innovative therapies) that resonate beyond this disease alone.
On convient de dire qu’une génération est nécessaire pour faire émerger une nouvelle famille de médicaments. L’amyotrophie spinale infantile (SMA), après l’élucidation du gène causal en 1995, dispose ...depuis peu de deux classes innovantes de thérapeutiques : l’administration répétée d’oligonucléotides antisens et l’administration unique d’une thérapie génique par scAAV9-SMN. En s’adressant aux mécanismes génétiques de la maladie, elles en modifient fondamentalement le cours. Ces avancées majeures dans une maladie extrêmement sévère, mortelle souvent avant l’âge de 18 mois dans les formes de type 1 (50 % des malades), ouvrent la voie pour d’autres pathologies graves du système nerveux ou neuromusculaire, et apportent une preuve déterminante de l’efficacité de ces classes nouvelles de produits appelés à s’adresser à de nombreuses maladies génétiques ou acquises. Elles génèrent aussi de nouvelles questions d’ordre scientifique et technologique (capacités limitées de production des quantités nécessaires en thérapie génique) mais également d’ordre éthique (conditions d’accès des malades à ces thérapies innovantes), qui résonnent au-delà de cette seule maladie.
It is worth stating that a generation is needed to bring about a new family of drugs. After the deciphering of the genetic cause in 1995, two innovative classes of therapeutics are now available for spinal muscular atrophy (SMA): the repeated administration of antisens oligonucleotides and the one-shot administration of a scAAV9-SMN as a gene therapy. By addressing the genetic mechanisms of the disease, these drugs fundamentally change its course. These major advances in an extremely severe disease, often fatal before the age of 18 months in the type 1 form (50% of patients), pave the way for the treatment of other serious pathologies of the nervous or neuromuscular system, and provide unambiguous evidence of the effectiveness of these new classes of drugs called to address a number of genetic or acquired diseases. These breakthroughs raise also new scientific and technological questions (limited production yields of gene therapy drugs) but also ethical issues (access of patients to these innovative therapies) that resonate beyond this disease alone.
Biothérapies Braun, Serge
M.S. Médecine sciences,
03/2019, Volume:
35, Issue:
Hors série n° 1
Journal Article
Peer reviewed
Open access
Les premiers biomédicaments conçus pour traiter des maladies neuromusculaires sont déjà sur le marché. Ils ne constituent pourtant que la partie émergée d’un iceberg considérable. Les développements ...en cours sont foisonnants, pour la thérapie génique comme cellulaire. L’AFM-Téléthon contribue depuis plusieurs décennies à impulser cette dynamique, qui n’est pas sans générer de nouveaux défis.
Les premiers biomédicaments conçus pour traiter des maladies neuromusculaires sont déjà sur le marché. Ils ne constituent pourtant que la partie émergée d’un iceberg considérable. Les développements ...en cours sont foisonnants, pour la thérapie génique comme cellulaire. L’AFM-Téléthon contribue depuis plusieurs décennies à impulser cette dynamique, qui n’est pas sans générer de nouveaux défis.
Nine patients with Duchenne or Becker muscular dystrophy were injected via the radialis muscle with a full-length human dystrophin plasmid, either once with 200 or 600 microg of DNA or twice, 2 weeks ...apart, with 600 microg of DNA. In the biopsies taken 3 weeks after the initial injection, the vector was detected at the injection site in all patients. Immunohistochemistry and nested reverse transcription-polymerase chain reaction indicated dystrophin expression in six of nine patients. The level of expression was low (up to 6% weak, but complete sarcolemmal dystrophin staining, and up to 26% partial sarcolemmal labeling). No side effects were observed, nor any cellular or humoral anti-dystrophin responses. These results suggest that exogenous dystrophin expression can be obtained in Duchenne/Becker patients after intramuscular transfer of plasmid, without adverse effects, hence paving the way for future developments in gene therapy of hereditary muscular diseases.
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