La tecnolog\u00eda CRISPR\/Cas9 es una herramienta molecular utilizada para \u201ceditar\u201d o \u201ccorregir\u201d el genoma de cualquier c\u00e9lula. Eso incluye, claro est\u00e1, a las c\u00e9lulas humanas. Ser\u00eda algo as\u00ed como unas tijeras moleculares que son capaces de cortar cualquier mol\u00e9cula de ADN haci\u00e9ndolo adem\u00e1s de una manera muy precisa y totalmente controlada. Esa capacidad de cortar el ADN es lo que permite modificar su secuencia, eliminando o insertando nuevo ADN.<\/p>\n
Las siglas CRISPR\/Cas9 provienen de\u00a0Clustered Regularly Interspaced Short Palindromic Repeats<\/em>, en espa\u00f1ol \u201c<\/em>Repeticiones Palindr\u00f3micas Cortas Agrupadas y Regularmente interespaciadas.\u201d La segunda es el nombre de una serie de prote\u00ednas, principalmente unas nucleasas, que las llamaron as\u00ed por\u00a0CRISPR associated system<\/em>\u00a0(es decir: \u201csistema asociado a CRISPR\u201d).<\/p>\n La revista The Scientist<\/strong>\u00a0 ha publicado la puesta en marcha de esta tecnolog\u00eda en dos pacientes una de ellas con Mieloma Multiple y una con Sarcoma, las cuales ser\u00edan las primeras en recibir las c\u00e9lulas modificas gen\u00e9ticamente en el estudio.\u00a0 El estudio es la primera instancia de pacientes en los Estados Unidos tratados con una terapia basada en CRISPR.<\/p>\n Adem\u00e1s de las aplicaciones para el c\u00e1ncer, los investigadores est\u00e1n explorando el uso de la llamada edici\u00f3n CRISPR ex vivo, en la cual las c\u00e9lulas se alteran fuera del cuerpo y luego se administran a los pacientes, para tratar trastornos sangu\u00edneos como la \u03b2-talasemia y la anemia de c\u00e9lulas falciformes. Otros equipos est\u00e1n trabajando para desarrollar terapias que editar\u00edan genes culpables en enfermedades gen\u00e9ticas dentro de los cuerpos de los pacientes.<\/p>\n D<\/span>octors have infused cells edited using CRISPR-Cas9 into two patients in a trial conducted at the University of Pennsylvania,\u00a0NPR<\/em><\/a>\u00a0reports today (April 16). A university spokesperson confirmed in an emailed statement to\u00a0The Scientist<\/em>\u00a0that the\u00a0trial<\/a>\u00a0is underway and that two patients, one with multiple myeloma and one with sarcoma, have been treated so far. The study is the first instance of patients in the US being treated with a CRISPR-based therapy.<\/p>\n In an interview with\u00a0The Scientist<\/em>\u00a0in June 2018, the leader of the study, oncologist\u00a0Edward Stadtmauer<\/a>, explained that CRISPR would be used as a tool in a new type of immunotherapy. His team would filter T cells from the blood of eligible patients with cancer, then use the gene-editing technique to knock out three of the cells\u2019 existing receptors and with a lentiviral vector insert the gene for a receptor called NY-ESO-1, a protein that appears on the surface of some cancer cells. The modified cells would then be expanded for a few weeks in the lab. Patients would receive a brief course of chemotherapy, after which the cells would be infused back into them.<\/p>\n In addition to cancer applications, researchers are exploring the use of so-called ex vivo CRISPR editing\u2014in which cells are altered outside the body and then given to patients\u2014to treat blood disorders such as \u03b2-thalassemia and sickle cell anemia. Other teams are working to develop therapies that would edit genes at fault in genetic diseases inside patients\u2019 bodies.<\/p>\n S<\/span>ince its debut less than a decade ago, CRISPR-Cas9 gene editing has inspired its share of grandiose and cautionary forecasts: that we might soon be able to resurrect beasts from the ancient past, for example, or (that classic genetic manipulation controversy) create designer babies. While such applications may never see the light of day, the technology is already revolutionizing genetics research, allowing scientists to easily manipulate model organisms in the lab. Moreover, many biomedical scientists see the system as a means to fix problematic DNA at play in countless genetic diseases.<\/p>\n Scientists and companies at the front lines of developing CRISPR-based therapies have started with relatively modest goals, targeting rare single-gene disorders and largely aiming to transplant modified cells rather than set a gene-editing delivery system loose in the body. But if green-lighted by regulators, such therapies could serve as trial balloons for a much broader use of CRISPR in medicine.<\/p>\n \u201cUp to now, gene therapy has consisted of trying to get [new copies of] genes into cells in people\u2019s bodies, and that\u2019s been tough,\u201d says\u00a0David Flannery<\/a>, a medical geneticist at the Cleveland Clinic. CRISPR, instead, offers a way to tweak genes already present in their cells.<\/p>\n CRISPR ex vivo<\/strong><\/p>\n With the\u00a0approval<\/a>\u00a0of Novartis\u2019s Kymriah last year, the US Food and Drug Administration (FDA) for the first time green-lighted a treatment\u2014in this case, a cancer immunotherapy\u2014consisting of genetically modified cells. A patient\u2019s own T cells are extracted from the blood and treated with a virus that inserts a gene for a chimeric antigen receptor (CAR). The resulting CAR T cells are then expanded and infused back into the body. Ex vivo CRISPR-based therapies now in development take a similar approach.<\/p>\n University of Pennsylvania oncologist\u00a0Edward Stadtmauer<\/a>\u00a0is starting a\u00a0Phase 1 trial<\/a>\u00a0testing a therapy that will filter T cells from the blood of eligible patients with cancer, then use CRISPR to knock out three of the cells\u2019 existing T-cell receptors (TCR\u03b1, TCR\u03b2, and PD-1) and a lentiviral vector to insert a receptor for NY-ESO-1, a protein that appears on the surface of some cancer cells. After the modified cells have been expanded for a few weeks and patients have received a brief course of chemotherapy, researchers will infuse the cells, says Stadtmauer, who is currently recruiting patients to the trial.<\/p>\n CRISPR-based cancer immunotherapies are also in the pipeline of the Switzerland-based company CRISPR Therapeutics, which has announced its plans to file an investigational new drug (IND) application with the FDA for one such therapy by the end of this year. As in the UPenn trial, that therapy is based on knocking out T-cell receptors and adding a CAR programmed to seek out a cancer-associated surface protein\u2014in this case, CD19. But in contrast to UPenn\u2019s approach, the company plans to use cells from healthy donors and remove the major histocompatibility complex 1, a modification that researchers at the firm hope will enable the treatment to be used on multiple patients without provoking an immune response.<\/p>\n The patient cells used in autologous CAR-T therapies have been repeatedly exposed to antigen and inflammatory signals. As a result, they \u201coften are pretty beat up, they\u2019re exhausted, and they\u2019re often not able to expand when they see the antigens,\u201d explains\u00a0Tony Ho<\/a>, the company\u2019s head of research and development. \u201cWith our technology we can make . . . a universal off-the-shelf [treatment]\u201d that uses cells from a healthy person to avoid that shortcoming.<\/p>\n Beyond cancer, CRISPR Therapeutics aims to use ex vivo CRISPR editing to treat blood disorders such as \u03b2-thalassemia and sickle cell anemia. The idea is to extract hematopoietic stem cells from patients\u2019 blood and edit them to make fetal hemoglobin as a workaround for the defective adult hemoglobin at fault in both disorders. The company applied for permission from European regulators in December to begin a Phase 1\/2 clinical trial for \u03b2-thalassemia and plans to treat its first patient there later this year, but its plans to debut the same treatment in US trials to treat sickle cell anemia were put on hold in May when the FDA requested answers to additional questions during its review of the IND.<\/p>\n In a more direct approach to treating sickle cell anemia,\u00a0Matthew Porteus<\/a>, a physician-researcher at Stanford University, and his team have been working to fix the causative mutation in hematopoietic stem cells. Because the disease is caused by a single-nucleotide mutation, \u201con a chalkboard, it would be easy to say, \u2018If we could change that back to something that doesn\u2019t cause disease, we could cure the disease,\u2019\u201d he says.<\/p>\n In the lab, the team has used CRISPR and homology-directed repair (HDR), which supplies a bit of DNA to cells to use as a template when repairing CRISPR\u2019s double-strand breaks, to correct mutations in 60 percent to 80 percent of patient cells, which Porteus expects will be more than enough for the therapy to alleviate symptoms of the disease. The next step will be to infuse the edited cells back into patients, where they\u2019re expected to naturally lodge themselves in the marrow and begin producing healthy red blood cells. Porteus estimates that a clinical trial on the treatment could begin by the middle of next year. Ultimately, he hopes to treat not just sickle cell, but also other genetic diseases of the blood, including \u03b2-thalassemia. \u201cIf we\u2019re successful, we believe we will have the platform to apply it to hundreds of other diseases without even having to change very much,\u201d he says.<\/p>\n Genome editing researcher\u00a0Jacob Corn<\/a>\u00a0of the University of California, Berkeley, is also using HDR to tackle sickle cell disease, with an eye on other diseases centered on hematopoietic stem cells. He likens his group\u2019s approach to performing precision \u201csurgery\u201d on a patient\u2019s genome, with edits customized to each person\u2019s mutation. Corn, who cofounded the gene editing\u2013based biotech company\u00a0Spotlight Therapeutics<\/a>\u00a0and receives honoraria from or owns stock in several others, is hoping to launch a clinical trial for sickle cell disease as early as next year.<\/p>\n \u201cThere are a lot of really exciting results coming out every day,\u201d Corn says. Although no such treatment has hit the market yet, \u201cI\u2019m optimistic that given even a decade, we\u2019re going to see widespread [therapeutic] gene editing.\u201d<\/p>\n Cambridge, Massachusetts\u2013based Intellia Therapeutics has ex vivo therapies in the preclinical pipeline for cancer and sickle cell disease, but its most advanced program is actually an in vivo treatment. Using lipid nanoparticles to deliver the CRISPR machinery to hepatocytes of patients with transthyretin amyloidosis, researchers hope to disable the mutated allele encoding transthyretin. The protein doesn\u2019t play an important role in the body, and an abnormal version of it can form deposits in the peripheral, and sometimes in the autonomic, nervous system, leading to loss of sensation in the extremities and, in the latter case, impairments of physiological functions. \u201c[Transthyretin] has a minor function in the body, ordinarily, and so if you have this amyloidosis which is killing you, it\u2019s just much better to get rid of the protein entirely,\u201d says\u00a0Tom Barnes<\/a>, a senior vice president at Intellia. \u201cOur therapy is designed to knock out both copies.\u201d A one-time treatment is showing\u00a0sustained results<\/a>\u00a0in mice, he says, and the company aims to file an IND late next year.<\/p>\n A potential pitfall of injecting CRISPR into the body is the risk of provoking an immune reaction. At Cambridge, Massachusetts\u2013based Editas Medicine, a five-year-old pharma company whose cofounders include the Broad Institute\u2019s Feng Zhang and Harvard University\u2019s George Church, researchers are hoping to avoid such issues by delivering CRISPR for genetic eye diseases directly to the eyes, organs that are immunoprivileged and are less likely to become inflamed in reaction to the therapy.<\/p>\n The treatment furthest along in the pipeline targets one form of Leber congenital amaurosis, a genetic disease that causes vision loss or blindness. In the subtype of the disease that Editas is targeting, a point mutation in an intron causes abnormal splicing of the\u00a0CEP290<\/em>\u00a0transcript. The aim of the therapy is to snip out the mutation via nonhomologous end joining (NHEJ), a DNA repair process that doesn\u2019t involve a template. At the American Society of Gene & Cell Therapy meeting in May, an Editas researcher\u00a0presented<\/a>\u00a0results from macaques showing the treatment was well tolerated and successfully edited the\u00a0CEP290<\/em>\u00a0gene, and the firm announced plans to file an IND application very soon. \u201cWe believe that if we restore the CEP290 protein, we\u2019ll restore the [function of the eye\u2019s photoreceptors] and thereby significantly improve vision in these patients that are heavily visually impaired, if not blind,\u201d explains Chief Scientific Officer Charlie Albright.<\/p>\n Editas is also applying lessons learned from the development of its Leber congenital amaurosis therapy in programs to treat other inherited eye diseases, such as Usher\u2019s syndrome 2a, as well as blindness-causing herpes simplex virus\u20131 infection, Albright says.<\/p>\n FUENTE:\u00a0The Scientist<\/a>\u00a0,\u00a0Dciencia<\/a>\u00a0,\u00a0The Scientist<\/a><\/p>\n","protected":false},"excerpt":{"rendered":" Avances en la tecnolog\u00eda CRISPR\/Cas9: La tecnolog\u00eda CRISPR\/Cas9 es una herramienta molecular utilizada para \u201ceditar\u201d o \u201ccorregir\u201d el genoma de […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_exactmetrics_skip_tracking":false,"_exactmetrics_sitenote_active":false,"_exactmetrics_sitenote_note":"","_exactmetrics_sitenote_category":0,"footnotes":""},"categories":[716],"tags":[],"class_list":["post-12049","post","type-post","status-publish","format-standard","hentry","category-cientificas-fr"],"_links":{"self":[{"href":"https:\/\/www.fundacionisabelgemio.com\/fr\/wp-json\/wp\/v2\/posts\/12049","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.fundacionisabelgemio.com\/fr\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.fundacionisabelgemio.com\/fr\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.fundacionisabelgemio.com\/fr\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.fundacionisabelgemio.com\/fr\/wp-json\/wp\/v2\/comments?post=12049"}],"version-history":[{"count":0,"href":"https:\/\/www.fundacionisabelgemio.com\/fr\/wp-json\/wp\/v2\/posts\/12049\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.fundacionisabelgemio.com\/fr\/wp-json\/wp\/v2\/media?parent=12049"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.fundacionisabelgemio.com\/fr\/wp-json\/wp\/v2\/categories?post=12049"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.fundacionisabelgemio.com\/fr\/wp-json\/wp\/v2\/tags?post=12049"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}Art\u00edculo publicado por la Revista The Scientist :<\/h3>\n
One person with multiple myeloma and one with sarcoma are the first so far to receive the genetically engineered T cells in the study.<\/h4>\n
CRISPR in situ<\/h4>\n