La guida definitiva all'editing genico.
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Glossario

94 termini usati in tutto il CRISPR Atlas, ciascuno definito in un linguaggio semplice. I termini tecnici presenti nel sito rimandano a questa pagina.

94 termini mostrati

ABCDEFGHIKLMNOPRSTVWZ

A

Adenine

One of the four DNA letters, written A. It pairs with thymine.

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Adeno-associated virus (AAV)

A small virus, harmless in itself, widely modified into a delivery vehicle for genetic medicines. Usually abbreviated AAV. Its cargo limit of about 4.7 kilobases is a major constraint.

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Allele

One of the alternative versions of a gene at a given location. You inherit one from each parent.

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Allogeneic

Coming from a donor rather than the patient. Allogeneic cell therapies are made in advance and given off the shelf, which requires gene editing to stop the donor cells attacking the recipient.

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Amino acid

One of the building blocks that proteins are made from. Each set of three DNA letters specifies one amino acid.

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Apheresis

A procedure that separates and collects specific cells from a person's blood, returning the rest. It is how stem cells are collected for editing.

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Autologous

Coming from the patient's own body. Autologous cell therapies are manufactured individually for each person.

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B

Base editing

Changing one DNA letter into another chemically, without cutting both strands of the helix.

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Base pair

Two DNA letters bonded across the double helix: A with T, or G with C. Genome sizes are measured in base pairs.

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Biologics licence application (BLA)

Biologics licence application — the submission a company makes to the FDA seeking approval to market a biological medicine.

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Boxed warning

The most serious warning a medicines regulator can require on a product label, reserved for risks prescribers must be explicitly told about.

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Bystander edit

An unintended change to a second editable letter that happens to sit inside a base editor's small working window, next to the one you meant to change.

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C

CRISPR

Clustered Regularly Interspaced Short Palindromic Repeats — a bacterial immune system reprogrammed into a tool for finding and changing chosen DNA.

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CRISPR array

The stretch of a bacterial genome where fragments of past viral invaders are stored between repeated sequences — the original biological CRISPR.

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CRISPRa

Using a disabled CRISPR protein to increase a gene's expression, without changing its sequence.

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CRISPRi

Using a disabled CRISPR protein to block a gene from being read, without changing its sequence.

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Cas12

A family of CRISPR proteins that cut DNA leaving staggered ends and recognise a different sequence signal from Cas9. Also used in diagnostics.

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Cas13

A CRISPR protein that targets RNA rather than DNA, so its effect is temporary and the genome is untouched.

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Cas9

The best-known CRISPR protein. Guided by an RNA, it cuts both strands of DNA at a chosen site.

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Chromatin

DNA together with the proteins it is packaged with. How tightly it is packed affects whether a gene can be read at all.

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Chromosome

One long DNA molecule packaged with proteins. Humans normally have 46, in 23 pairs.

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Clinical hold

An order from a regulator suspending or restricting a clinical trial, usually after a safety concern. Holds can be lifted once the concern is addressed.

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Collateral cleavage

The habit some CRISPR proteins have of cutting nearby genetic material indiscriminately once activated. A problem inside cells and the basis of CRISPR diagnostics.

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Conditioning

Chemotherapy or antibody treatment given before a cell therapy to clear space in the bone marrow so edited cells can engraft. It is the source of most of the risk in ex vivo therapies.

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Cytosine

One of the four DNA letters, written C. It pairs with guanine.

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D

DNA

Deoxyribonucleic acid — the molecule that stores genetic instructions, written in an alphabet of four letters.

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Deletion

The loss of one or more DNA letters. If the number lost is not a multiple of three it shifts the reading frame and usually destroys the protein.

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Dominant

An inheritance pattern in which one faulty copy of a gene is enough to cause the condition.

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Double strand break

A cut through both strands of the DNA helix. Ordinary CRISPR makes these deliberately; base and prime editing were invented to avoid them.

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E

Editing window

The small stretch of DNA, usually four or five letters, within which a base editor can act. Anything editable inside it may be changed.

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Engraftment

When transplanted cells take hold in the body and begin producing new cells. The first milestone after any cell therapy.

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Enhancer

A stretch of DNA that increases how strongly a gene is expressed, often from a distance. The approved sickle cell therapy targets an enhancer, not a gene.

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Epigenetic editing

Deliberately writing or erasing those marks at a chosen gene, to change its expression without altering sequence.

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Epigenetics

Chemical marks on DNA and its packaging proteins that change how genes are read without changing the sequence itself. Cells copy these marks when they divide.

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Ex vivo

Editing performed on cells outside the body, which are then returned to the patient.

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Exon

A part of a gene retained in the final message and usually translated into protein.

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F

Fetal haemoglobin

The form of haemoglobin made before birth. It does not sickle, which is why switching it back on treats sickle cell disease.

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Frameshift

A shift in how DNA is read in groups of three, caused by inserting or deleting a number of letters not divisible by three. It usually destroys the protein.

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G

Gene

A stretch of DNA carrying the instructions for one product, usually a protein.

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Gene drive

An engineered genetic element designed to spread through a wild population far faster than normal inheritance would allow.

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Gene editing

Changing DNA that is already present in a cell, at a chosen location.

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Gene therapy

Treating disease by delivering genetic material. In its classic form it adds a working copy of a gene rather than changing the existing one.

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Genome

The complete set of genetic material in an organism.

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Genotype

The genetic makeup of an individual, as distinct from the observable characteristics it produces.

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Germline

Cells that can pass genetic information to children — eggs, sperm and embryos. Editing them would be heritable, and is prohibited or unapproved for clinical use in most countries.

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Good manufacturing practice (GMP)

Good manufacturing practice — the quality standard cell and gene therapy products must be made under.

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Guanine

One of the four DNA letters, written G. It pairs with cytosine.

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Guide rna

The short RNA molecule that tells a CRISPR protein where to act. Changing it is how the system is reprogrammed.

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H

Haploinsufficiency

When one working copy of a gene is not enough for normal function — a situation better suited to turning expression up than to correcting sequence.

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Homology-directed repair (HDR)

Homology-directed repair — the precise repair pathway that can copy a supplied template into a break. It works only in dividing cells and is inefficient.

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Hypoimmune

Engineered to avoid recognition by the immune system, so that transplanted cells can survive without immunosuppressive drugs.

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I

In vivo

Editing performed inside the body, usually by infusion or injection, rather than on cells outside it.

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Indel

A small insertion or deletion, the usual result of a cell repairing a CRISPR cut by end joining.

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Insertion

The addition of one or more DNA letters into a sequence.

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Insertional mutagenesis

Harm caused when inserted genetic material lands inside or beside an important gene and disrupts it.

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Intron

A part of a gene removed from the message before the protein is made. Faults in introns can still cause disease by disrupting how the message is assembled.

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K

Knockdown

Reducing the amount of a gene's product without eliminating it, usually temporarily.

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Knockout

Disabling a gene so it no longer produces a working product. The most reliable thing gene editing does.

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L

Lipid nanoparticle

A microscopic fat bubble carrying genetic cargo into cells. The delivery technology behind in vivo CRISPR and mRNA vaccines; it goes efficiently to the liver.

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M

Missense

A change of one DNA letter that alters which amino acid is used, giving a protein that is present but altered.

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Mosaicism

When some cells in an organism carry a change and others do not. It is a serious problem in embryo editing, where it means the result cannot be controlled or fully known.

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Multiplex editing

Making several edits in the same cell at once. Necessary for off-the-shelf cell therapy, and riskier than a single edit.

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Mutation

A change in DNA sequence. Most have no effect; a minority cause disease.

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N

Nickase

A modified Cas protein that cuts only one strand of DNA. Used in base and prime editors to avoid a full break.

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Non-homologous end joining (NHEJ)

Non-homologous end joining — the fast, always-available, error-prone repair pathway that usually seals a CRISPR cut and disables the gene.

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Nonsense

A change that creates a premature stop signal, ending a protein early and usually destroying its function.

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Nucleotide

One unit of DNA or RNA: a sugar, a phosphate and one of the four bases. The letters of the genetic alphabet.

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O

Off target

An edit made somewhere other than the intended site, because the guide tolerated a mismatch. Measured empirically, not assumed absent.

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Orphan designation

A regulatory status for treatments aimed at rare diseases, carrying incentives intended to make small-population development viable.

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P

PAM

Protospacer-adjacent motif — a short sequence that must sit next to the target or Cas9 will not cut. It is a real constraint on where you can edit.

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Phenotype

The observable characteristics of an organism, resulting from its genes and its environment.

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Point mutation

A change affecting a single DNA letter. The most common kind of disease-causing variant, and the reason base editing was invented.

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Prime editing

Writing a chosen new stretch of DNA sequence into a specific site, without cutting both strands and without a separate donor template.

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Promoter

The stretch of DNA where the machinery that reads a gene first binds. Its accessibility largely determines whether the gene is expressed.

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Protein

The molecular machines that do most of the work in cells. Genes are the instructions for making them.

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R

RNA

Ribonucleic acid — the single-stranded working copy a cell makes when it needs to use a gene.

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RNA interference (RNAi)

RNA interference — using short RNA molecules to have the cell destroy a specific message, lowering a protein's level temporarily.

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Recessive

An inheritance pattern in which both copies of a gene must be faulty for the condition to appear.

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Recombinase

An enzyme that cuts and rejoins DNA at specific recognition sites, able to insert large sequences.

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Ribonucleoprotein

The editing protein and its guide RNA delivered together as a ready-made complex. It acts quickly and then degrades, which limits off-target opportunity.

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S

Somatic

Affecting the body's ordinary cells rather than eggs, sperm or embryos. Somatic changes are not inherited, and all approved gene editing is somatic.

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Splicing

Removing introns and joining exons to make the final message. Many disease-causing variants act by disrupting it.

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Surrogate endpoint

A measurement used as a stand-in for the outcome that actually matters — a blood marker rather than survival. It may or may not predict real benefit.

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T

TALEN

Transcription activator-like effector nuclease — an earlier editing tool built from protein modules, each recognising one DNA letter.

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Thymine

One of the four DNA letters, written T. It pairs with adenine.

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Transgene

A gene deliberately introduced into an organism, as distinct from one that was already there.

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Transposase

An enzyme that moves a segment of DNA from one place in the genome to another.

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V

Variant of uncertain significance

Variant of uncertain significance — a genetic change that has been found but whose effect, if any, is not known.

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Vector

Anything used to carry genetic material into cells — a modified virus, a lipid nanoparticle, or a piece of engineered DNA.

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W

Wild type

The typical, unaltered version of a gene or organism, used as the reference for comparison.

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Z

Zinc finger nuclease

The first programmable gene-editing tool used in people, built from small protein modules that each grip about three DNA letters.

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D

dCas9

A version of Cas9 that can still find its target but cannot cut. It is the foundation of base editors, prime editors and gene-regulation tools.

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P

pegRNA

The guide used in prime editing, which carries both the target address and the replacement sequence to be written.

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T

tracrRNA

A small RNA discovered by Emmanuelle Charpentier that is required for CRISPR-Cas9 to function; fused with the targeting RNA it forms the single guide RNA.

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