How CRISPR lets us edit our DNA | Jennifer Doudna
Summary
TLDRJennifer Doudna, junto a Emmanuelle Charpentier, desarrolló la tecnología CRISPR-Cas9, que permite editar genomas con precisión. Esta herramienta nació de un estudio sobre cómo las bacterias combaten las infecciones virales. CRISPR ha mostrado promesa en curar enfermedades genéticas y en la modificación de embriones humanos, lo que conlleva cuestiones éticas. Doudna aboga por una conversación global antes de avanzar, destacando la importancia de considerar los impactos de esta tecnología revolucionaria.
Takeaways
- 🧬 La tecnología CRISPR-Cas9 permite a los científicos realizar cambios en el ADN de las células, lo que podría curar enfermedades genéticas.
- 🔍 CRISPR surge de un proyecto de investigación básica para descubrir cómo las bacterias luchan contra las infecciones virales.
- ⏱ Las bacterias utilizan un sistema inmunitario adaptativo llamado CRISPR para detectar y destruir el ADN viral.
- 🛡 La parte del sistema CRISPR que es la proteína Cas9 busca, corta y degrada el ADN viral de manera específica.
- 🧰 La función de Cas9 fue adaptada para ser usada como tecnología de ingeniería genética, permitiendo la eliminación o inserción precisa de fragmentos de ADN en las células.
- 🐁 CRISPR ha sido utilizada en animales como ratones y monos, y recientemente, científicos chinos cambiaron genes en embriones humanos.
- 🏥 Los científicos en Filadelfia utilizaron CRISPR para eliminar el ADN del virus HIV de células humanas infectadas.
- 🤔 La edición genómica con CRISPR plantea cuestiones éticas, especialmente cuando se aplica a embriones y puede afectar a especies, incluyendo la nuestra.
- 🌐 La investigadora Jennifer Doudna ha llamado a una conversación global sobre la tecnología CRISPR para considerar sus implicaciones éticas y sociales.
- 📈 Aunque la tecnología CRISPR es relativamente nueva, se espera que en las próximas décadas se vean aplicaciones clínicas en humanos, especialmente en el tratamiento de enfermedades genéticas.
Q & A
¿Qué es la tecnología CRISPR-Cas9 y qué permite hacer?
-La tecnología CRISPR-Cas9 es un sistema de edición de genomas que permite a los científicos realizar cambios en el ADN de las células, lo que podría permitir curar enfermedades genéticas.
¿Cómo surgió la tecnología CRISPR?
-La tecnología CRISPR surgió de un proyecto de investigación básica centrada en descubrir cómo las bacterias luchan contra las infecciones virales.
¿Qué es el sistema inmunitario adaptativo CRISPR en las bacterias?
-El sistema CRISPR es un mecanismo inmunitario adaptativo en bacterias que les permite detectar y destruir el ADN viral.
¿Qué función cumple la proteína Cas9 en el sistema CRISPR?
-La proteína Cas9 busca, corta y eventualmente degrada el ADN viral de una manera específica dentro del sistema CRISPR.
¿En qué se puede utilizar la tecnología CRISPR para la medicina?
-CRISPR se puede utilizar para curar enfermedades genéticas, como la fibrosis quística o la anemia falciforme, editando el ADN de las células afectadas.
¿Han habido aplicaciones de CRISPR en seres humanos?
-Sí, científicos chinos han utilizado CRISPR para cambiar genes en embriones humanos, y en Filadelfia se ha demostrado que se puede usar para eliminar el ADN del virus VIH de células humanas infectadas.
¿Qué problemas éticos surgen con la posibilidad de editar genomas?
-La edición de genomas puede llevar a la creación de 'humanos diseñados' con características mejoradas, lo que plantea cuestiones éticas sobre la manipulación de la herencia humana.
¿Por qué Jennifer Doudna y sus colegas han pedido una conversación global sobre CRISPR?
-Para considerar todas las implicaciones éticas y sociales de una tecnología como CRISPR, especialmente en cuanto a su uso en embriones y su impacto en la especie humana.
¿Cuál es la posición de Jennifer Doudna sobre la pausa en la aplicación clínica de CRISPR en embriones humanos?
-Doudna y sus colegas han pedido una pausa en cualquier aplicación clínica de CRISPR en embriones humanos para tener tiempo de reflexionar sobre las implicaciones de hacerlo.
¿Qué se espera de la reunión en diciembre sobre la tecnología CRISPR?
-Se espera que la reunión permita exponer las opiniones de diversos interesados y reflexionar sobre cómo usar la tecnología de manera responsable.
¿Cómo Jennifer Doudna ve la posibilidad de que la tecnología CRISPR se use para mejoras en lugar de solo terapias?
-Doudna reconoce que CRISPR puede usarse para mejorar características humanas, pero subraya la importancia de considerar cuidadosamente las consecuencias éticas y sociales antes de proceder.
Outlines
🧬 Invenciones en la edición genómica con CRISPR-Cas9
Jennifer Doudna y su colega Emmanuelle Charpentier desarrollaron una tecnología revolucionaria para editar genomas llamada CRISPR-Cas9. Esta herramienta permite a los científicos realizar cambios precisos en el ADN de las células, lo que podría abocar a curar enfermedades genéticas. La tecnología surgió de un proyecto de investigación básica centrada en cómo las bacterias combaten las infecciones virales. Las bacterias utilizan un sistema inmunitario adaptativo conocido como CRISPR para detectar y destruir el ADN viral. Doudna y su equipo descubrieron que el proteina Cas9, parte del sistema CRISPR, podía ser utilizado para eliminar o insertar fragmentos específicos de ADN en las células con una precisión extraordinaria. La tecnología CRISPR ha sido utilizada para modificar el ADN en ratones, monos y hasta en embriones humanos, y para eliminar el virus VIH de las células humanas infectadas. Sin embargo, la capacidad de realizar ediciones genómicas plantea cuestiones éticas significativas, especialmente en embriones, lo que ha llevado a Doudna a llamar a una conversación global sobre el uso de esta tecnología.
✂️ Cómo funciona la tecnología CRISPR-Cas9
La tecnología CRISPR-Cas9 funciona utilizando un complejo formado por RNA y la proteína Cas9, que actúa como una tijera capaz de cortar el ADN en doble helix. Este complejo es programable y puede ser diseñado para reconocer secuencias de ADN específicas y realizar cortes en esas posiciones. La capacidad de la célula para detectar y reparar el ADN dañado es clave para la ingeniería genómica, ya que permite que las células reparen los cortes o incorporen información genética nueva. Esto puede ser utilizado para corregir mutaciones que causan enfermedades como la fibrosis quística o la enfermedad de Huntington. Aunque la ingeniería genómica no es nueva, la simplicidad y eficiencia de CRISPR la hacen especialmente atractiva. La tecnología CRISPR ha sido probada en modelos animales de enfermedades humanas, como ratones y monos, y se está investigando cómo controlar la reparación del ADN y limitar los efectos no deseados después de su uso.
🚀 Perspectivas y desafíos de la aplicación clínica de CRISPR
Jennifer Doudna anticipa que las aplicaciones clínicas de la tecnología CRISPR se materializarán en adultos en un plazo de aproximadamente 10 años, con posibles ensayos clínicos y terapias aprobadas en ese horizonte. La tecnología ha generado un gran interés en la comunidad empresarial y de inversión, con la creación de startups y la inversión de capital de riesgo. Sin embargo, la posibilidad de utilizar CRISPR para mejorar características humanas, como el aumento de la resistencia a enfermedades o cambios en características físicas, plantea preguntas éticas significativas. Doudna y sus colegas han pedido una pausa en la aplicación clínica de CRISPR en embriones humanos para considerar cuidadosamente las implicaciones. Esta posición se basa en la necesidad de una discusión global sobre el uso responsable de la tecnología, similar a la pausa en el uso de la clonación molecular en los años 70. La responsabilidad de considerar tanto las consecuencias no intencionadas como las intencionadas de un avance científico es crucial.
🌐 La importancia de la regulación y la responsabilidad en la ciencia
Jennifer Doudna reflexiona sobre la responsabilidad de los científicos en la creación y el uso de tecnologías con implicaciones éticas, como la edición genómica con CRISPR. Ella reconoce el desafío de involucrarse en debates fuera del laboratorio, pero argumenta que la posición de los científicos en la génesis de la tecnología CRISPR los coloca en una posición de responsabilidad. Doudna expresa su deseo de que otras tecnologías sean consideradas de la misma manera, y sugiere que la discusión sobre CRISPR podría servir como un modelo para otros campos científicos. La conversación en la comunidad científica y la regulación son cruciales para abordar los desafíos éticos y de seguridad que conlleva la innovación tecnológica.
Mindmap
Keywords
💡CRISPR-Cas9
💡Genoma
💡Cas9
💡RNA
💡Infección viral
💡Genoma editado
💡Células madre
💡Etica
💡Enfermedades genéticas
💡Desarrollo exponencial
Highlights
Inventaron una nueva tecnología para editar genomas llamada CRISPR-Cas9.
CRISPR permite a los científicos realizar cambios en el ADN de las células para curar enfermedades genéticas.
La tecnología CRISPR surgió de un proyecto de investigación básica sobre cómo las bacterias combaten las infecciones virales.
Las bacterias tienen un sistema inmune adaptativo llamado CRISPR que les permite detectar y destruir el ADN viral.
El sistema CRISPR incluye una proteína llamada Cas9 que busca y degrada el ADN viral de manera específica.
La función de Cas9 fue adaptada como tecnología de ingeniería genética para insertar o eliminar segmentos específicos de ADN en las células.
CRISPR ha sido utilizada para cambiar el ADN en células de ratas, monos y seres humanos.
Los científicos chinos han utilizado CRISPR para modificar genes en embriones humanos.
CRISPR ha sido empleado para eliminar el ADN del virus VIH de células humanas infectadas.
La edición genómica con CRISPR plantea cuestiones éticas que deben considerarse, especialmente en embriones.
Se ha llamado a una conversación global sobre la tecnología CRISPR para abordar sus implicaciones éticas y sociales.
El sistema CRISPR permite a las células registrar y transmitir a futuras generaciones los virus a los que han estado expuestas.
CRISPR-Cas9 funciona como un complejo de RNA y proteína que busca y corta el ADN viral en la célula.
El complejo CRISPR-Cas9 es programable y puede ser dirigido a reconocer secuencias específicas de ADN para realizar cortes precisos.
La capacidad de las células para reparar el ADN roto se puede utilizar para corregir mutaciones que causan enfermedades.
CRISPR es más sencillo que las tecnologías de ingeniería genética anteriores y permite la edición genómica con facilidad.
Se esperan aplicaciones clínicas de CRISPR en adultos en los próximos 10 años, incluyendo ensayos clínicos y terapias aprobadas.
La tecnología CRISPR ha generado interés en startups y capital de riesgo, pero también plantea preguntas éticas sobre mejoras humanas.
Se ha pedido una pausa en la aplicación clínica de CRISPR en embriones humanos para considerar sus implicaciones.
CRISPR ha pasado de la ficción científica a la realidad, con aplicaciones en animales y plantas, y conlleva una gran responsabilidad.
Transcripts
A few years ago,
with my colleague, Emmanuelle Charpentier,
I invented a new technology for editing genomes.
It's called CRISPR-Cas9.
The CRISPR technology allows scientists to make changes
to the DNA in cells
that could allow us to cure genetic disease.
You might be interested to know
that the CRISPR technology came about through a basic research project
that was aimed at discovering how bacteria fight viral infections.
Bacteria have to deal with viruses in their environment,
and we can think about a viral infection like a ticking time bomb --
a bacterium has only a few minutes to defuse the bomb
before it gets destroyed.
So, many bacteria have in their cells an adaptive immune system called CRISPR,
that allows them to detect viral DNA and destroy it.
Part of the CRISPR system is a protein called Cas9,
that's able to seek out, cut and eventually degrade viral DNA
in a specific way.
And it was through our research
to understand the activity of this protein, Cas9,
that we realized that we could harness its function
as a genetic engineering technology --
a way for scientists to delete or insert specific bits of DNA into cells
with incredible precision --
that would offer opportunities
to do things that really haven't been possible in the past.
The CRISPR technology has already been used
to change the DNA in the cells of mice and monkeys,
other organisms as well.
Chinese scientists showed recently
that they could even use the CRISPR technology
to change genes in human embryos.
And scientists in Philadelphia showed they could use CRISPR
to remove the DNA of an integrated HIV virus
from infected human cells.
The opportunity to do this kind of genome editing
also raises various ethical issues that we have to consider,
because this technology can be employed not only in adult cells,
but also in the embryos of organisms,
including our own species.
And so, together with my colleagues,
I've called for a global conversation about the technology that I co-invented,
so that we can consider all of the ethical and societal implications
of a technology like this.
What I want to do now is tell you what the CRISPR technology is,
what it can do,
where we are today
and why I think we need to take a prudent path forward
in the way that we employ this technology.
When viruses infect a cell, they inject their DNA.
And in a bacterium,
the CRISPR system allows that DNA to be plucked out of the virus,
and inserted in little bits into the chromosome --
the DNA of the bacterium.
And these integrated bits of viral DNA get inserted at a site called CRISPR.
CRISPR stands for clustered regularly interspaced short palindromic repeats.
(Laughter)
A big mouthful -- you can see why we use the acronym CRISPR.
It's a mechanism that allows cells to record, over time,
the viruses they have been exposed to.
And importantly, those bits of DNA are passed on to the cells' progeny,
so cells are protected from viruses not only in one generation,
but over many generations of cells.
This allows the cells to keep a record of infection,
and as my colleague, Blake Wiedenheft, likes to say,
the CRISPR locus is effectively a genetic vaccination card in cells.
Once those bits of DNA have been inserted into the bacterial chromosome,
the cell then makes a little copy of a molecule called RNA,
which is orange in this picture,
that is an exact replicate of the viral DNA.
RNA is a chemical cousin of DNA,
and it allows interaction with DNA molecules
that have a matching sequence.
So those little bits of RNA from the CRISPR locus
associate -- they bind -- to protein called Cas9,
which is white in the picture,
and form a complex that functions like a sentinel in the cell.
It searches through all of the DNA in the cell,
to find sites that match the sequences in the bound RNAs.
And when those sites are found --
as you can see here, the blue molecule is DNA --
this complex associates with that DNA
and allows the Cas9 cleaver to cut up the viral DNA.
It makes a very precise break.
So we can think of the Cas9 RNA sentinel complex
like a pair of scissors that can cut DNA --
it makes a double-stranded break in the DNA helix.
And importantly, this complex is programmable,
so it can be programmed to recognize particular DNA sequences,
and make a break in the DNA at that site.
As I'm going to tell you now,
we recognized that that activity could be harnessed for genome engineering,
to allow cells to make a very precise change to the DNA
at the site where this break was introduced.
That's sort of analogous
to the way that we use a word-processing program
to fix a typo in a document.
The reason we envisioned using the CRISPR system for genome engineering
is because cells have the ability to detect broken DNA
and repair it.
So when a plant or an animal cell detects a double-stranded break in its DNA,
it can fix that break,
either by pasting together the ends of the broken DNA
with a little, tiny change in the sequence of that position,
or it can repair the break by integrating a new piece of DNA at the site of the cut.
So if we have a way to introduce double-stranded breaks into DNA
at precise places,
we can trigger cells to repair those breaks,
by either the disruption or incorporation of new genetic information.
So if we were able to program the CRISPR technology
to make a break in DNA
at the position at or near a mutation causing cystic fibrosis, for example,
we could trigger cells to repair that mutation.
Genome engineering is actually not new, it's been in development since the 1970s.
We've had technologies for sequencing DNA,
for copying DNA,
and even for manipulating DNA.
And these technologies were very promising,
but the problem was that they were either inefficient,
or they were difficult enough to use
that most scientists had not adopted them for use in their own laboratories,
or certainly for many clinical applications.
So, the opportunity to take a technology like CRISPR and utilize it has appeal,
because of its relative simplicity.
We can think of older genome engineering technologies
as similar to having to rewire your computer
each time you want to run a new piece of software,
whereas the CRISPR technology is like software for the genome,
we can program it easily, using these little bits of RNA.
So once a double-stranded break is made in DNA,
we can induce repair,
and thereby potentially achieve astounding things,
like being able to correct mutations that cause sickle cell anemia
or cause Huntington's Disease.
I actually think that the first applications of the CRISPR technology
are going to happen in the blood,
where it's relatively easier to deliver this tool into cells,
compared to solid tissues.
Right now, a lot of the work that's going on
applies to animal models of human disease, such as mice.
The technology is being used to make very precise changes
that allow us to study the way that these changes in the cell's DNA
affect either a tissue or, in this case, an entire organism.
Now in this example,
the CRISPR technology was used to disrupt a gene
by making a tiny change in the DNA
in a gene that is responsible for the black coat color of these mice.
Imagine that these white mice differ from their pigmented litter-mates
by just a tiny change at one gene in the entire genome,
and they're otherwise completely normal.
And when we sequence the DNA from these animals,
we find that the change in the DNA
has occurred at exactly the place where we induced it,
using the CRISPR technology.
Additional experiments are going on in other animals
that are useful for creating models for human disease,
such as monkeys.
And here we find that we can use these systems
to test the application of this technology in particular tissues,
for example, figuring out how to deliver the CRISPR tool into cells.
We also want to understand better
how to control the way that DNA is repaired after it's cut,
and also to figure out how to control and limit any kind of off-target,
or unintended effects of using the technology.
I think that we will see clinical application of this technology,
certainly in adults,
within the next 10 years.
I think that it's likely that we will see clinical trials
and possibly even approved therapies within that time,
which is a very exciting thing to think about.
And because of the excitement around this technology,
there's a lot of interest in start-up companies
that have been founded to commercialize the CRISPR technology,
and lots of venture capitalists
that have been investing in these companies.
But we have to also consider
that the CRISPR technology can be used for things like enhancement.
Imagine that we could try to engineer humans
that have enhanced properties, such as stronger bones,
or less susceptibility to cardiovascular disease
or even to have properties
that we would consider maybe to be desirable,
like a different eye color or to be taller, things like that.
"Designer humans," if you will.
Right now, the genetic information
to understand what types of genes would give rise to these traits
is mostly not known.
But it's important to know
that the CRISPR technology gives us a tool to make such changes,
once that knowledge becomes available.
This raises a number of ethical questions that we have to carefully consider,
and this is why I and my colleagues have called for a global pause
in any clinical application of the CRISPR technology in human embryos,
to give us time
to really consider all of the various implications of doing so.
And actually, there is an important precedent for such a pause
from the 1970s,
when scientists got together
to call for a moratorium on the use of molecular cloning,
until the safety of that technology could be tested carefully and validated.
So, genome-engineered humans are not with us yet,
but this is no longer science fiction.
Genome-engineered animals and plants are happening right now.
And this puts in front of all of us a huge responsibility,
to consider carefully both the unintended consequences
as well as the intended impacts of a scientific breakthrough.
Thank you.
(Applause)
(Applause ends)
Bruno Giussani: Jennifer, this is a technology with huge consequences,
as you pointed out.
Your attitude about asking for a pause or a moratorium or a quarantine
is incredibly responsible.
There are, of course, the therapeutic results of this,
but then there are the un-therapeutic ones
and they seem to be the ones gaining traction,
particularly in the media.
This is one of the latest issues of The Economist -- "Editing humanity."
It's all about genetic enhancement, it's not about therapeutics.
What kind of reactions did you get back in March
from your colleagues in the science world,
when you asked or suggested
that we should actually pause this for a moment and think about it?
Jennifer Doudna: My colleagues were actually, I think, delighted
to have the opportunity to discuss this openly.
It's interesting that as I talk to people,
my scientific colleagues as well as others,
there's a wide variety of viewpoints about this.
So clearly it's a topic that needs careful consideration and discussion.
BG: There's a big meeting happening in December
that you and your colleagues are calling,
together with the National Academy of Sciences and others,
what do you hope will come out of the meeting, practically?
JD: Well, I hope that we can air the views
of many different individuals and stakeholders
who want to think about how to use this technology responsibly.
It may not be possible to come up with a consensus point of view,
but I think we should at least understand
what all the issues are as we go forward.
BG: Now, colleagues of yours,
like George Church, for example, at Harvard,
they say, "Yeah, ethical issues basically are just a question of safety.
We test and test and test again, in animals and in labs,
and then once we feel it's safe enough, we move on to humans."
So that's kind of the other school of thought,
that we should actually use this opportunity and really go for it.
Is there a possible split happening in the science community about this?
I mean, are we going to see some people holding back
because they have ethical concerns,
and some others just going forward
because some countries under-regulate or don't regulate at all?
JD: Well, I think with any new technology, especially something like this,
there are going to be a variety of viewpoints,
and I think that's perfectly understandable.
I think that in the end,
this technology will be used for human genome engineering,
but I think to do that without careful consideration and discussion
of the risks and potential complications
would not be responsible.
BG: There are a lot of technologies and other fields of science
that are developing exponentially, pretty much like yours.
I'm thinking about artificial intelligence, autonomous robots and so on.
No one seems --
aside from autonomous warfare robots --
nobody seems to have launched a similar discussion in those fields,
in calling for a moratorium.
Do you think that your discussion may serve as a blueprint for other fields?
JD: Well, I think it's hard for scientists to get out of the laboratory.
Speaking for myself,
it's a little bit uncomfortable to do that.
But I do think that being involved in the genesis of this
really puts me and my colleagues in a position of responsibility.
And I would say that I certainly hope that other technologies
will be considered in the same way,
just as we would want to consider something that could have implications
in other fields besides biology.
BG: Jennifer, thanks for coming to TED.
JD: Thank you.
(Applause)
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