A

Allele-specific silencing – Designing an ASO to target only one version of a gene while leaving the other untouched.
Antisense oligonucleotide (ASO) – A short synthetic DNA or RNA molecule designed to bind RNA and change how a gene works.

Antagomirs – A short synthetic molecules designed to bind to and block microRNAs, so those microRNAs cannot regulate their target genes.

ALS (Amyotrophic Lateral Sclerosis) –A progressive neurodegenerative disease that damages motor neurons in the brain and spinal cord, causing loss of muscle control and weakness.  

AMD (Age-related macular degeneration) – A common eye disease, usually in older adults, that damages the macula (the central part of the retina), causing loss of central vision leading to blurry vision. 

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B

Backbone chemistry – The chemical structure that links nucleotides together in an ASO.
Base pairing – The matching of nucleotides (A–T/U, C–G) that allows ASOs to bind RNA.

Biodistribution – The pattern of where a drug or therapeutic molecule travels and accumulates in the body (organs, tissues, and cells) after administration, and how those levels change over time.

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C

Charge-neutral ASO – An ASO with no electrical charge, which can reduce toxicity and immune activation.

Cas enzyme (CRISPR-associated enzyme) – A protein used by CRISPR systems that is guided (usually by a CRISPR RNA/guide RNA) to a specific nucleic acid sequence, where it performs an action such as cutting DNA or RNA, processing CRISPR RNAs, or binding and regulating the target.
Chimeric ASO – An ASO made of mixed chemical regions (e.g., gapmer design).
Conjugated ASO – An ASO linked to another molecule (such as GalNAc or peptides) to improve delivery.

CRISPR/Cas – A genome-editing system where a guide RNA directs a Cas enzyme (often Cas9) to a specific DNA sequence so it can be cut and then repaired, enabling targeted changes to the genome.

COL6 RD (collagen VI–related disorders) – A group of inherited muscle and connective tissue conditions caused by variants in collagen VI genes (COL6A1, COL6A2, COL6A3), typically including Ullrich congenital muscular dystrophy and Bethlem myopathy, with muscle weakness and joint contractures/hyperlaxity.

CRISPR KO (CRISPR knockout)– A CRISPR edit designed to inactivate a gene—usually by creating small insertions/deletions during DNA repair that disrupt the reading frame or introduce an early stop codon, preventing functional protein production.

Conjugates– Engineered molecules made by chemically linking two components (e.g., an oligonucleotide or drug linked to a peptide, lipid, or antibody fragment) to improve delivery, targeting, stability, or potency.

Chimeric – Describes a molecule, cell, or organism made from parts of different origins—e.g., a chimeric protein combining domains from different proteins, or a chimeric antibody with sequences from different species.

Cis-elements –  Regulatory sequence motifs located on the same nucleic acid molecule as the gene they control (DNA or RNA), such as promoters/enhancers in DNA or splicing enhancers/silencers in pre-mRNA that influence expression or processing.

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D

Delivery vehicle – A method or molecule used to help ASOs enter cells.
ddPCR (droplet digital PCR) –A highly sensitive method that partitions a PCR reaction into thousands of droplets to enable absolute quantification of DNA/RNA copies (useful for low-level changes, rare variants, or precise fold-change measurements).

DMD (Duchenne muscular dystrophy) –A severe X-linked muscle-wasting disease caused by pathogenic variants in the DMD gene leading to absent or near-absent dystrophin, resulting in progressive muscle weakness, loss of ambulation, and later heart/respiratory complications.

DM1 (myotonic dystrophy type 1) – An inherited multisystem disorder caused by a CTG repeat expansion in the DMPK gene, characterized by myotonia (delayed muscle relaxation), muscle weakness, and involvement of other systems (e.g., heart conduction, endocrine, cataracts).

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E

Exon skipping – Using ASOs to cause cells to skip a faulty exon when making RNA.
Exon inclusion – Using ASOs to force inclusion of an exon that is normally skipped.

Ex vivo –Experiments performed on cells, tissues, or organs removed from a living organism and studied outside the body under controlled conditions.

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F

FD (Frontotemporal Dementia) –A group of neurodegenerative disorders affecting the frontal and temporal lobes, causing progressive changes in behavior/personality and/or language, and sometimes movement symptoms.

Fully modified RNA/DNA hybrids –Synthetic oligonucleotides that combine RNA- and DNA-like building blocks with extensive chemical modifications to improve stability, binding, and biological activity.

 

G

Gapmer – A common ASO design with a DNA “gap” that activates RNase H, flanked by modified nucleotides for stability.
GalNAc – A sugar molecule attached to ASOs to target liver cells.
Gene silencing – Reducing gene expression by targeting RNA.

gRNA (guide RNA) – A short RNA molecule that guides a gene-editing enzyme, such as Cas9, to a specific DNA sequence so it can make a targeted change.

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H

Hybridization affinity – How tightly an ASO binds its RNA target.

Fully modified RNA/DNA hybrids - Oligonucleotides made of both RNA and DNA building blocks, where the sugars and/or backbone have been chemically modified throughout the whole sequence to improve stability, binding, and therapeutic performance.

Hypomorphic variants – Genetic variants that reduce, but do not eliminate, gene function, leading to partial loss of protein activity or expression.

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I

Immune stimulation – Activation of the immune system by certain ASO chemistries (an unwanted side effect).

Isoform modulation.

In silico – performed using computer models or simulations rather than in the laboratory or in living organisms.

Isoform modulation –Shifting which transcript/protein isoform a gene produces (often by changing splicing or polyadenylation) to increase a beneficial isoform or reduce a harmful one.

Inherited metabolic diseases (IMD) –A broad group of genetic disorders caused by enzyme or transporter defects that disrupt normal metabolism, often leading to toxic metabolite buildup or energy deficiency.

iPSC (induced pluripotent stem cells) –Adult cells reprogrammed back to a stem-cell state so they can be expanded and differentiated into many cell types for disease modeling and therapy research.

Intronic variants –DNA changes located in introns that can affect gene regulation or splicing (e.g., by creating/disrupting splice signals), even though they are not in coding exons.

In vivo –Experiments performed in a living organism (e.g., mouse studies or human clinical studies).

In vitro –Experiments performed outside a living organism, typically in cells, tissues, or biochemical systems in the lab.

IRD (Inherited retinal disease) – A genetically diverse group of disorders that cause progressive retinal dysfunction and vision loss.

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L

LNA (Locked Nucleic Acid) – A chemically “locked” nucleotide that increases ASO binding strength and stability.

LSDs (Lysosomal Storage Diseases) – Inherited disorders where lysosomal dysfunction causes accumulation of undegraded material in cells.

Ligand – A molecule that binds specifically to a target (often a receptor or protein) to trigger, block, or modulate its function.

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M

Mismatch tolerance – How well an ASO can still bind its target if there is a sequence difference.
Morpholino – A type of ASO with a neutral backbone that does not activate RNase H.

Mixmer chemistry – An oligonucleotide design that mixes different nucleotide chemistries within the same strand (e.g., DNA + modified RNA) to tune affinity, stability, and mechanism.

miRNA (microRNA) –  Small endogenous RNAs that regulate gene expression by binding target mRNAs and reducing their translation and/or stability.

Minigenes – Engineered DNA constructs containing selected exons/introns used to study splicing and test how variants or antisense oligos alter exon inclusion.

MPS III (Mucopolysaccharidosis type III / Sanfilippo syndrome) – A lysosomal storage disease caused by impaired heparan sulfate degradation, leading to progressive neurodegeneration.

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O

Off-target hybridization – ASO binding to unintended RNA sequences.

Organoids –3D mini-tissues grown from stem cells that mimic key structural and functional features of an organ for modeling development and disease.

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P

PMO (Phosphorodiamidate Morpholino Oligomer) – A neutral, synthetic ASO commonly used for exon skipping.

PPMO (Peptide-conjugated PMO) – A PMO linked to a cell-penetrating peptide to improve delivery into cells, especially muscle.

Phosphorothioate (PS) – A backbone modification where sulfur replaces oxygen to increase stability and protein binding.

Peptide Nucleic Acid (PNA) – A synthetic oligonucleotide analog with a peptide-like backbone that binds strongly to DNA/RNA and is highly resistant to nucleases, but can require delivery strategies to enter cells.

Pseudoexon insertion – Aberrant inclusion of an intronic sequence as a new “exon” in the mature mRNA, usually caused by intronic variants that create or strengthen splice signals.

PKU (phenylketonuria) –An inherited metabolic disease caused by deficient phenylalanine hydroxylase activity, leading to elevated phenylalanine and risk of neurotoxicity without treatment.

Propionic acidemia – An inherited metabolic disease due to deficiency of propionyl-CoA carboxylase, causing accumulation of toxic metabolites and episodes of metabolic decompensation.

PK (pharmacokinetics) – What the body does to a drug—its absorption, distribution, metabolism, and excretion over time (drug concentration vs. time).

PD (pharmacodynamics) – What the drug does to the body—its biological effects, mechanism of action, and the relationship between concentration and effect.

Phage – A bacteriophage, a virus that infects bacteria, commonly used as a tool in molecular biology (e.g., phage display for selecting binding peptides/antibodies).

Pipeline – The set of therapies or candidates in development, typically organized by stage (discovery, preclinical, clinical phases, regulatory review).

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R

RNase H – An enzyme that degrades RNA when it is bound by a DNA-like ASO.
RNA cleavage – Cutting of RNA molecules, often triggered by RNase H.

Repeat expansion –A mutation where a short DNA repeat (e.g., CTG, CAG, GAA) becomes abnormally long, often causing disease by toxic RNA/protein effects or gene silencing.

Retinitis pigmentosa  – an inherited eye disease that causes progressive vision loss due to retinal damage.

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S​

saRNA (small activating RNA) – A short RNA molecule that increase the expression of a specific gene by activating its transcription.

Steric blocking ASO – An ASO that blocks RNA processing without destroying the RNA.
Splice-switching oligonucleotide (SSO) – An ASO designed to change RNA splicing patterns.
Sequence specificity – How precisely an ASO recognizes its target RNA.

Splice regulatory sequences – Short RNA motifs (cis-elements) that enhance or repress splicing at nearby splice sites, influencing whether an exon is included or skipped.

siRNA (small interfering RNA) –Short double-stranded RNAs that guide the RNA interference pathway to degrade complementary mRNA, reducing expression of a target gene.

Splicing –The process of removing introns from pre-mRNA and joining exons to produce a mature mRNA, enabling alternative exon combinations in many genes.

Spinocerebellar ataxias – A group of inherited neurodegenerative disorders characterized by progressive incoordination (ataxia), often due to genetic variants including repeat expansions. 

snRNA (small nuclear RNA) –Short RNAs found in the cell nucleus that form the core of spliceosomal particles (snRNPs) and help remove introns from pre-mRNA during splicing.

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T

Target engagement – Proof that an ASO binds its intended RNA in cells or tissues.
tcDNA (Tricyclo-DNA) – A chemically constrained ASO with very high binding strength and stability.

Therapeutic exon skipping – Clinical use of ASOs to restore protein function.

Translation blocking – An oligonucleotide mechanism that inhibits protein production by preventing ribosome initiation or progression on an mRNA without necessarily degrading the mRNA.

Trans-elements – Diffusible factors (usually proteins or RNAs) that act on target RNAs/DNAs elsewhere—e.g., splicing factors that bind cis-elements to regulate splicing.

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U

Uncharged backbone – ASO chemistry lacking electrical charge, reducing immune activation.

U snRNA–based antisense RNAs – Engineered small nuclear RNAs (often derived from U1 or U7) that carry an antisense sequence to bind a target pre-mRNA and redirect splicing (e.g., promote exon skipping or correct abnormal splice-site use).

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W

Watson–Crick base pairing – The fundamental rule that allows ASOs to bind RNA.​

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Z

Zwitterionic ASO – ASOs containing both positive and negative charges to improve delivery and reduce toxicity.