Scientific and translational terminology for research, development, and collaboration
Numerals
- 2′-F (2′-fluoro modification) - A chemical modification in which the hydroxyl group at the 2′ position of a ribose sugar is replaced by fluorine. It can increase binding affinity and improve nuclease resistance. Used in selected oligonucleotide designs to tune stability and affinity.
- 2′-O-methoxyethyl (2′-MOE) modification - A ribose modification used in several therapeutic oligonucleotides to improve stability, binding affinity, and pharmacological properties. Commonly used in the flanking regions of gapmer ASOs.
- 2′-O-methyl (2′-OMe) modification - A ribose modification in which a methyl group is attached to the 2′ oxygen. It is commonly used to improve nuclease resistance and modulate binding properties. Used in selected ASOs and other oligonucleotide modalities.
A
ADME (absorption, distribution, metabolism, and excretion) - The processes that determine how a therapeutic agent enters the body, distributes across tissues, is chemically modified or degraded, and is eliminated. ADME studies help characterize ASO exposure, distribution, and clearance.
AGO2 (Argonaute 2) - A protein within the RNA-induced silencing complex that can cleave a target RNA when guided by a sufficiently complementary siRNA. AGO2 is central to siRNA activity and helps distinguish RNAi from ASO mechanisms.
Allele-specific silencing - The preferential inhibition of one version, or allele, of a gene while limiting effects on the other allele. This strategy can be useful when a disease is caused by a dominant pathogenic variant. ASOs can be designed to preferentially suppress a pathogenic allele.
Alternative splicing - The regulated production of different RNA transcripts from the same gene through the selective inclusion or exclusion of exons or the use of alternative splice sites. Splice-switching ASOs can redirect alternative splicing.
Antagomir - A chemically modified anti-miR designed to inhibit a microRNA. Antagomirs are a chemically modified subclass of anti-miR oligonucleotides.
Anti-miR - An oligonucleotide designed to bind and inhibit a selected microRNA, preventing the microRNA from regulating its target RNAs. Anti-miRs are antisense-based molecules that inhibit microRNAs.
Antibody–oligonucleotide conjugate (AOC) - An oligonucleotide linked to an antibody or antibody-derived targeting component to improve delivery to selected tissues or cell types. AOCs are being explored to improve delivery of ASOs and other oligonucleotides.
Antigene oligonucleotide - An oligonucleotide designed to bind a specific DNA sequence and modulate gene expression or another DNA-associated process. Antigene strategies are distinct from conventional ASO approaches, which primarily target RNA. Unlike conventional ASOs, antigene oligonucleotides target DNA rather than RNA.
Antisense - A nucleic-acid sequence designed to bind a complementary nucleic-acid target through hybridization.
Aptamer - A structured single-stranded DNA or RNA oligonucleotide selected for its ability to bind a specific molecular target, such as a protein. Aptamers are distinct from ASOs because they bind targets through their three-dimensional structure.
ASGPR (asialoglycoprotein receptor) - A receptor expressed at high levels on hepatocytes. It is widely used for liver-directed delivery of GalNAc-conjugated oligonucleotides. ASGPR is used for hepatocyte delivery of GalNAc-conjugated oligonucleotides.
ASO (antisense oligonucleotide) - A short, usually chemically modified, single-stranded oligonucleotide designed to bind a complementary RNA sequence and modulate gene expression..
B
Backbone chemistry - The chemical structure of the linkages connecting nucleotides within an oligonucleotide. Backbone modifications can affect stability, protein binding, cellular uptake, biodistribution, and tolerability. Backbone chemistry strongly influences ASO stability, uptake, and tolerability.
Biodistribution - The distribution of a therapeutic agent across organs, tissues, cells, and intracellular compartments over time. Biodistribution determines which tissues and cells are exposed to an ASO.
Blood–brain barrier (BBB) - A specialized barrier that limits the entry of many therapeutic agents into the central nervous system. Strategies to improve oligonucleotide delivery across or around the BBB are an active area of research.The BBB is a major challenge for ASO delivery to the central nervous system.
C
Cell-penetrating peptide (CPP) - A peptide designed to improve cellular uptake or tissue delivery of a linked therapeutic cargo. CPPs can be conjugated to oligonucleotides, including PMOs. CPPs can be conjugated to ASOs or PMOs to improve delivery.
Cellular uptake - The internalization of an oligonucleotide by a cell. Total cellular uptake does not necessarily indicate that the oligonucleotide reaches its pharmacological target. ASO uptake is necessary but does not guarantee productive intracellular delivery.
Chemical modification - A change introduced into an oligonucleotide’s backbone, sugar, nucleobase, or terminal groups to modify properties such as nuclease resistance, binding affinity, pharmacokinetics, potency, or tolerability. ASO properties are routinely optimized through chemical modifications.
Chimeric oligonucleotide - An oligonucleotide composed of regions with different chemical properties or functions. Gapmer ASOs are a common example.
circRNA (circular RNA) - An RNA molecule in which the 5′ and 3′ ends are covalently joined to form a closed loop. Circular RNAs can regulate biological processes, serve as therapeutic targets, or be engineered as therapeutic platforms. circRNAs can be targets for ASOs.
Clinical development - The stage of therapeutic development in which a candidate is evaluated in humans.
CMC (chemistry, manufacturing, and controls) - The activities used to define, manufacture, characterize, and control the quality of a therapeutic product throughout development and commercialization.
Conjugated oligonucleotide - An oligonucleotide chemically linked to another molecule, such as a sugar, peptide, lipid, or antibody-derived component, to modify tissue targeting, cellular uptake, intracellular trafficking, stability, or potency. ASOs can be conjugated to sugars, peptides, lipids, or antibody-derived components.
CpG motif - A cytosine–phosphate–guanine sequence motif that can contribute to immune stimulation in certain oligonucleotide contexts. CpG motifs may be considered during ASO sequence optimization because they can contribute to immune stimulation.
CRISPR (clustered regularly interspaced short palindromic repeats) - A family of gene-editing systems in which a guide RNA directs a CRISPR-associated enzyme, such as Cas9, to a selected nucleic-acid sequence. CRISPR can be used to validate ASO targets and study ASO-related pathways.
CRISPR knockout (CRISPR KO) - A genome-editing strategy designed to disrupt gene function, often by introducing insertions or deletions that create a frameshift or premature stop codon. CRISPR KO can be used to identify genes that influence ASO activity, trafficking, or toxicity.
D
Delivery vehicle - A formulation or carrier used to transport an oligonucleotide to its target tissue or cell type. Examples include lipid nanoparticles and other nanoscale delivery systems. Delivery vehicles may improve ASO tissue exposure or cellular entry.
Dose–response relationship - The relationship between the administered dose of a therapeutic agent and the magnitude of its biological or clinical effect.
E
Efficacy - The ability of a therapeutic intervention to produce its intended beneficial effect under defined experimental or clinical conditions.
Endosomal escape - The release of an internalized oligonucleotide from an endosomal compartment into the cytosol or nucleus, where it can reach its pharmacological target. Endosomal escape is an important barrier to the activity of many oligonucleotide therapeutics. Endosomal escape is a major barrier to the activity of many ASOs.
Endosomal trafficking - The movement and sorting of internalized molecules through intracellular compartments, including early endosomes, recycling endosomes, late endosomes, and lysosomes. Endosomal trafficking influences the intracellular fate of internalized ASOs.
Endosomal-release enhancer - A molecule or platform designed to improve the release of an internalized oligonucleotide from endosomal compartments into the cytosol or nucleus. These enhancers are being explored to increase productive ASO delivery.
Exon exclusion - The absence of a selected exon from the mature RNA transcript. Splice-switching ASOs can be used to promote exon exclusion.
Exon inclusion - The incorporation of a selected exon into the mature RNA transcript during splicing. Splice-switching ASOs can be used to promote exon inclusion.
Exon skipping - The exclusion of a selected exon from the mature RNA transcript during splicing. Exon skipping is a therapeutic strategy used by selected splice-switching ASOs.
Extrahepatic delivery - Delivery of a therapeutic agent to tissues outside the liver. Expanding efficient oligonucleotide delivery beyond hepatocytes is a major objective in the field. Expanding ASO delivery beyond the liver is a major objective in the field.
Extrahepatic targeting - Strategies intended to deliver oligonucleotide therapeutics efficiently to tissues beyond the liver, such as muscle, the central nervous system, lung, skin, or immune cells. Extrahepatic targeting is important for ASO delivery to tissues such as muscle and the central nervous system.
F
Fully modified RNA/DNA hybrid - An oligonucleotide design that combines RNA-like and DNA-like building blocks and uses extensive chemical modification to improve stability, binding properties, or biological activity. This design can be used in steric-blocking or other antisense applications.
G
GalNAc (N-acetylgalactosamine) - A sugar-based targeting ligand commonly conjugated to oligonucleotides to promote uptake by hepatocytes through the ASGPR receptor. GalNAc conjugation is widely used for liver-directed oligonucleotide delivery.
Gapmer - A chimeric oligonucleotide containing a central DNA-like region flanked by chemically modified nucleotides. Gapmer ASOs recruit RNase H1 to cleave a complementary RNA target.
Gene editing - The targeted modification of genomic DNA or, in some platforms, RNA. Gene-editing approaches can be used to disrupt, correct, insert, remove, or regulate selected genetic sequences.
Gene silencing - A reduction in gene expression or in the abundance of a gene product. Many ASOs are designed to reduce the abundance of a selected RNA.
gRNA (guide RNA) - An RNA component that directs a CRISPR-associated enzyme to a selected nucleic-acid target.
H
Hybridization affinity - The strength of binding between an oligonucleotide and its complementary nucleic-acid target. Affinity is influenced by sequence composition, oligonucleotide length, and chemical modifications. ASO affinity must be balanced with specificity and tolerability.
Hybridization-dependent off-target effect - An unintended effect caused by partial or complete binding of an oligonucleotide to a nucleic-acid sequence other than the intended target. ASOs can affect unintended RNAs through partial complementarity.
Hybridization-independent effect - An unintended effect that does not primarily result from hybridization to an unintended nucleic-acid sequence. Such effects may be influenced by chemistry, protein interactions, dose, or delivery. ASO chemistry, dose, or protein interactions can contribute to these effects.
I
Immune activation - Activation of innate or adaptive immune responses by an oligonucleotide, its sequence, its chemistry, or its delivery system. Immune activation is generally monitored as a potential safety concern during therapeutic development. ASO sequence, chemistry, dose, and delivery method can influence immune activation.
Immunogenicity - The capacity of a therapeutic agent to trigger an immune response directed against the therapeutic or one of its components. Immunogenicity is related to, but distinct from, innate immune activation.
Innate immune sensing - Recognition of an oligonucleotide or delivery component by cellular immune sensors, potentially leading to inflammatory signaling. Innate immune sensing is evaluated during ASO optimization and safety assessment.
Intronic variant - A DNA variant located within an intron. Some intronic variants alter RNA splicing by creating or disrupting splice sites or regulatory sequences. ASOs can be designed to correct splicing defects caused by selected intronic variants.
iPSC (induced pluripotent stem cell) - A differentiated cell that has been reprogrammed into a pluripotent state and can be differentiated into multiple cell types for disease modeling or therapeutic research. iPSC-derived cells can provide disease-relevant models for ASO testing.
Isoform modulation - A change in the relative production of alternative RNA or protein isoforms. ASOs can modulate isoforms by influencing splicing or other RNA-processing events. ASOs can alter isoform production by redirecting RNA processing.
K
Knock-in - The targeted insertion or replacement of a genetic sequence at a selected genomic location.
Knockdown - A reduction in the expression of a gene or in the abundance of its RNA or protein product. Many ASOs are designed to achieve knockdown of a selected RNA.
Knockout (KO) - The disruption or inactivation of a gene in order to eliminate or substantially reduce its function.
L
Ligand - A molecule that binds a selected receptor or molecular target. In oligonucleotide delivery, ligands can be used to promote uptake by specific cell types. Ligands can be attached to ASOs to improve uptake by selected cell types.
Lipid nanoparticle (LNP) - A lipid-based delivery system used to encapsulate and transport nucleic-acid therapeutics. LNP composition influences biodistribution, cellular uptake, and intracellular release. LNPs may be investigated as delivery systems for selected ASO applications.
LNA (locked nucleic acid) - A chemically constrained nucleotide analog in which the ribose structure is locked into a specific conformation. LNA incorporation generally increases binding affinity for complementary RNA. LNA incorporation can increase the binding affinity of an ASO.
Long non-coding RNA (lncRNA) - An RNA transcript longer than approximately 200 nucleotides that does not encode a conventional protein. Some lncRNAs regulate cellular processes and can serve as targets for oligonucleotide-based therapies. Selected lncRNAs can be targeted with ASOs.
M
Medicinal chemistry - The design and optimization of therapeutic molecules to improve properties such as potency, selectivity, stability, delivery, pharmacokinetics, and tolerability. ASO medicinal chemistry optimizes sequence, length, and chemical modifications.
MicroRNA (miRNA) - A small endogenous regulatory RNA that contributes to post-transcriptional gene regulation by guiding a protein complex to selected RNA targets. miRNAs can be inhibited with anti-miR oligonucleotides.
Minigene assay - An experimental system using an engineered DNA construct containing selected exons and introns to study splicing and evaluate the effects of variants or splice-modulating oligonucleotides. Minigene assays are often used to evaluate splice-switching ASOs.
miRNA mimic - A synthetic oligonucleotide designed to reproduce or restore the activity of a selected microRNA.
miRNA replacement - A therapeutic strategy designed to restore or increase the activity of a selected microRNA, commonly by using a synthetic miRNA mimic. This approach uses miRNA mimics rather than conventional ASOs.
Mismatch - A non-complementary base pair between an oligonucleotide and a nucleic-acid sequence. The number and position of mismatches can affect both on-target activity and off-target interactions. Mismatch position and number can influence ASO specificity and potency.
Mixmer chemistry - An oligonucleotide design in which different nucleotide chemistries are interspersed within the same strand to tune affinity, stability, and mechanism of action. Mixmer ASOs can be designed to tune affinity and steric-blocking activity.
Morpholino - A nucleic-acid analog with a charge-neutral morpholine-based backbone. Morpholino oligonucleotides are commonly used for steric-blocking applications. See also: PMO. Morpholino oligonucleotides are used in steric-blocking ASO applications.
N
N-of-1 RNA therapy (n=1 RNA therapy) - An individualized RNA-targeted therapy designed for a single patient, or sometimes for a very small number of patients, with a specific disease-causing genetic variant. ASOs are among the most advanced modalities used in N-of-1 therapeutic development. Patient-specific ASOs are an important example of N-of-1 RNA therapy.
Nonsense-mediated decay (NMD) - A cellular RNA-surveillance pathway that degrades selected transcripts containing premature termination codons. Splice-modulating ASOs can change whether an RNA is susceptible to NMD.
Nuclease resistance - The ability of an oligonucleotide to resist degradation by enzymes that cleave nucleic acids. Chemical modifications are commonly introduced to improve nuclease resistance. Chemical modifications are used to protect ASOs from enzymatic degradation.
O
Off-target effect - An unintended biological effect caused by an oligonucleotide. Off-target effects can result from binding to unintended nucleic-acid sequences or from sequence-independent interactions associated with chemistry, dose, or delivery. ASO off-target effects can be sequence-dependent or sequence-independent.
Oligonucleotide - A short chain of nucleotides or nucleotide analogs. Oligonucleotides can be developed as therapeutic agents, diagnostics, or research tools. ASOs are one class of therapeutic oligonucleotides.
On-target activity - The intended biological effect resulting from interaction of an oligonucleotide with its selected molecular target.
Organoid - A three-dimensional cell-culture model that reproduces selected structural or functional features of an organ and can be used for disease modeling or therapeutic evaluation. Organoids can be used to evaluate ASO delivery, activity, or toxicity.
P
PD (pharmacodynamics) - The biological effects of a therapeutic agent and the relationship between drug exposure and response. ASO pharmacodynamic readouts may include RNA reduction or splice correction.
Peptide–oligonucleotide conjugate - An oligonucleotide linked to a peptide to improve cellular uptake, tissue delivery, intracellular trafficking, or another pharmacological property. Peptides can be attached to ASOs or PMOs to improve delivery.
Phosphodiester (PO) linkage - The naturally occurring internucleotide linkage found in DNA and RNA. Unmodified PO linkages are generally susceptible to degradation by nucleases. PO linkages may be incorporated selectively into ASO designs.
Phosphorothioate (PS) linkage - A backbone modification in which one non-bridging oxygen atom in a phosphodiester linkage is replaced by sulfur. PS linkages can improve nuclease resistance and influence protein binding, pharmacokinetics, cellular uptake, and tolerability. PS linkages are widely used in ASOs to improve stability and influence pharmacology.
Phosphorothioate DNA (PS-DNA) - A DNA-like oligonucleotide in which phosphorothioate linkages replace some or all natural phosphodiester linkages. This chemistry improves resistance to nuclease degradation and alters interactions with proteins. PS-DNA regions are commonly used in RNase H-active ASO designs.
Phosphorothioate stereochemistry - The stereochemical configuration created at phosphorothioate linkages. Control of this configuration can influence interactions with proteins, nucleases, and biological targets. PS stereochemistry can influence ASO pharmacological properties.
PK (pharmacokinetics) - The time-dependent behavior of a therapeutic agent in the body, including its absorption, distribution, metabolism, and elimination. ASO pharmacokinetics describe exposure over time in plasma and tissues.
PMO (phosphorodiamidate morpholino oligomer) - A charge-neutral morpholino oligonucleotide commonly used for steric-blocking applications, including therapeutic exon skipping. PMOs do not recruit RNase H1. PMOs are steric-blocking ASOs used in applications including exon skipping.
PNA (peptide nucleic acid) - A synthetic nucleic-acid analog with a charge-neutral peptide-like backbone. PNAs bind complementary nucleic-acid sequences with high affinity but often require delivery strategies to improve cellular uptake. PNAs can be used for antisense applications but often require delivery strategies.
PPMO (peptide-conjugated PMO) - A PMO linked to a peptide to improve cellular uptake or tissue delivery. PPMOs can increase potency but require careful evaluation of safety and tolerability. PPMOs are designed to improve PMO uptake and tissue delivery.
Preclinical development - The stage of therapeutic development in which a candidate is evaluated before human studies.
Premature termination codon (PTC) - A stop codon that occurs earlier than expected within a coding RNA sequence. Splice-modulating ASOs can sometimes bypass a PTC or alter nonsense-mediated decay.
Premature transcription termination (PTT) - The termination of RNA synthesis before a full-length transcript is produced. PTT may contribute to knockdown by some RNase H-active ASOs.
Productive delivery - Delivery that enables a therapeutic agent to reach the intracellular compartment containing its molecular target and produce the intended biological effect. For ASOs, productive delivery means reaching the compartment containing the RNA target.
Productive uptake - Cellular internalization that ultimately results in pharmacological activity. Only a fraction of internalized ASO may generate pharmacological activity.
Pseudoexon inclusion - The abnormal incorporation of an intronic sequence into mature RNA as if it were an exon. Disease-associated intronic variants can create or strengthen signals that promote pseudoexon inclusion. Splice-switching ASOs can be designed to suppress pathogenic pseudoexon inclusion.
R
Repeat expansion - An abnormal increase in the number of repeated DNA sequence units at a genomic locus. Repeat expansions can cause disease through altered gene expression, toxic RNA, or abnormal protein products. ASOs can be developed to reduce toxic repeat-containing RNAs.
Ribozyme - An RNA molecule with catalytic activity. Natural and engineered ribozymes can cleave or modify selected RNA targets.
RISC (RNA-induced silencing complex) - A protein complex involved in RNA interference. The guide strand of an siRNA directs RISC to a complementary RNA target, enabling sequence-dependent silencing. RISC is central to siRNA activity rather than conventional ASO mechanisms.
RNA interference (RNAi) - A sequence-specific gene-silencing mechanism in which small RNAs guide protein complexes to complementary RNA targets. RNAi is the mechanism used by siRNAs and is distinct from conventional ASO mechanisms.
RNA sequencing (RNA-seq) - A sequencing-based method used to measure and characterize RNA molecules within a sample. RNA-seq can evaluate ASO activity, splice changes, and potential off-target effects.
RNA stabilization - A therapeutic strategy designed to increase the abundance or lifespan of a selected RNA transcript, for example by blocking a degradation signal or an interaction that promotes RNA decay. Selected ASOs can stabilize RNA by blocking decay-promoting interactions.
RNase H - A family of enzymes that cleave the RNA strand of an RNA–DNA duplex. RNase H activity underlies the mechanism of DNA-like antisense oligonucleotides.
RNase H-mediated gene silencing - A mechanism in which an antisense oligonucleotide forms an RNA-DNA duplex with a complementary RNA target and recruits RNase H1, which cleaves the RNA strand and reduces transcript abundance. This is a major mechanism used by DNA-like gapmer ASOs.
RNase H1 - An RNase H enzyme that cleaves the RNA strand of an RNA-DNA duplex. RNase H1 is the principal enzyme recruited by gapmer ASOs.
S
Safety - The evaluation of risks associated with a therapeutic intervention, including adverse effects and dose-related toxicity. ASO safety assessment considers sequence, chemistry, dose, exposure, and unintended effects.
saRNA (small activating RNA) - A small RNA designed to increase the expression of a selected gene through RNA-mediated activation mechanisms.
Seed region - A short region within a small RNA guide strand that contributes strongly to target recognition. Seed-region complementarity can influence unintended interactions in RNA-interference applications. The seed region is particularly relevant to siRNA off-target effects rather than ASO design.
Sequence specificity - The extent to which an oligonucleotide selectively recognizes its intended nucleic-acid sequence rather than similar unintended sequences. Sequence specificity is central to ASO design and off-target assessment.
siRNA (small interfering RNA) - A short double-stranded RNA designed to reduce the expression of a selected gene through the RNA-interference pathway. After cellular processing, one strand guides RISC to a complementary RNA target. siRNAs are distinct from ASOs but are a major oligonucleotide-therapeutic modality.
Splice modulation - The alteration of RNA-splicing patterns using an oligonucleotide or another intervention. Splice modulation can promote exon inclusion, exon exclusion, exon skipping, correction of aberrant splicing, or changes in isoform production. Splice-modulating ASOs can promote exon inclusion, exclusion, or isoform changes.
Splice regulatory sequence - A short RNA sequence that influences splicing decisions by promoting or repressing recognition of nearby splice sites. Examples include exonic and intronic splicing enhancers and silencers. ASOs can bind splice regulatory sequences to redirect exon recognition.
Splice-switching oligonucleotide (SSO) - A steric-blocking oligonucleotide designed to alter RNA splicing. SSOs are ASOs that alter splicing through steric blocking.
Stereopure oligonucleotide - An oligonucleotide synthesized with defined stereochemistry at selected backbone linkages. Defined backbone stereochemistry can be explored to optimize selected ASO properties.
Steric-blocking oligonucleotide - An oligonucleotide that binds RNA and physically interferes with an RNA-dependent process without directly inducing cleavage of the target RNA. Steric-blocking ASOs can alter splicing or inhibit translation without cleaving RNA.
T
Target engagement - Evidence that a therapeutic agent interacts with its intended molecular target in a biological system. ASO target-engagement studies assess interaction with the intended RNA target.
Target specificity - The degree to which a therapeutic agent acts on its intended target while limiting interactions with unintended targets. Target specificity is a central consideration in ASO development.
Targeted delivery - The preferential delivery of a therapeutic agent to a selected tissue, cell type, or intracellular compartment. Targeted delivery strategies aim to improve ASO exposure in selected tissues or cells.
tcDNA (tricyclo-DNA) - A conformationally constrained nucleic-acid analog developed to improve binding affinity, stability, and pharmacological properties. tcDNA-based therapeutic approaches remain an active area of research. tcDNA is being investigated as an ASO chemistry.
Therapeutic index - The relationship between a therapeutic agent’s beneficial effects and its adverse effects. A wider therapeutic index generally provides a greater margin for safe and effective dosing. ASO optimization aims to increase efficacy while limiting adverse effects.
Tissue targeting - The preferential delivery or activity of a therapeutic agent in a selected tissue or cell type. Tissue targeting is a major objective in ASO development.
Tolerability - The extent to which a therapeutic agent can be administered without unacceptable adverse effects. ASO tolerability depends on factors including sequence, chemistry, dose, and tissue exposure.
Toxicology - The study of adverse effects caused by a substance or therapeutic candidate and the conditions under which those effects occur. ASO toxicology evaluates potential adverse effects related to sequence, chemistry, dose, and distribution.
Transferrin-receptor targeting - A delivery strategy that uses the transferrin receptor as an entry route into selected tissues or cell types. It is being explored for applications including muscle and central-nervous-system delivery. This strategy is being explored to improve ASO delivery to selected tissues.
Translation blocking - A steric-blocking mechanism in which an oligonucleotide inhibits protein synthesis by interfering with ribosome recruitment or progression on an RNA target. Some steric-blocking ASOs inhibit protein synthesis through this mechanism.
U
U7 snRNA-based antisense RNA - An engineered small nuclear RNA derived from U7 snRNA and modified to carry an antisense sequence. This approach can redirect splicing after delivery through a gene-transfer system and is distinct from administration of a synthetic ASO. This splice-modulation approach is related to, but distinct from, administration of a synthetic ASO.
X
XNA (xeno-nucleic acid) - A synthetic nucleic-acid analog containing a sugar, backbone, or nucleobase structure that differs from naturally occurring DNA and RNA. XNAs can be engineered to modify stability, affinity, or resistance to enzymatic degradation. Some XNA chemistries are explored for antisense applications.
Z
Zwitterionic oligonucleotide - An oligonucleotide containing both positive and negative charges. Zwitterionic designs are being explored as a way to modify delivery, protein interactions, pharmacokinetics, and tolerability. Zwitterionic ASO designs are being explored to modify delivery and tolerability.