Xenonucleic Acid (XNA)Any synthetic nucleic acid analog with a non-natural backbone that retains the ability to base-pair with DNA, RNA, or other XNAs and store genetic information.
TNAThreose Nucleic Acid -- XNA based on a four-carbon threose sugar. Simpler than DNA/RNA and a candidate for prebiotic genetic systems.
HNAHexitol Nucleic Acid -- XNA based on a six-carbon hexitol sugar ring, forming A-form helices with good nuclease stability.
FANA2'-Fluoro-Arabinonucleic Acid -- XNA with a fluorine atom at the 2' position of the arabinose sugar, excellent for XNAzyme catalysis and gene silencing.
LNALocked Nucleic Acid -- XNA with a methylene bridge locking the ribose in C3'-endo conformation, providing dramatically enhanced binding affinity (+2-8 degrees Celsius per base pair).
PNAPeptide Nucleic Acid -- XNA with a neutral peptide backbone instead of sugar-phosphate, completely resistant to nucleases and proteases.
MorpholinoA XNA type with a morpholine ring backbone and phosphorodiamidate linkages, used in FDA-approved splice-switching drugs for Duchenne muscular dystrophy.
NucleaseAn enzyme that degrades nucleic acids by cleaving phosphodiester bonds. XNA's resistance to nucleases is a key advantage for therapeutic applications.
Watson-Crick Base PairingThe specific hydrogen bonding between complementary nucleobases (A-T/U and G-C) that holds the two strands of a double helix together.
Oligonucleotide TherapeuticA drug based on short synthetic nucleic acid sequences (typically 15-30 nucleotides) that modulates gene expression through mechanisms like antisense, RNAi, or aptamer binding.
Antisense Oligonucleotide (ASO)A single-stranded nucleic acid that binds to complementary mRNA to block translation or trigger degradation, thereby silencing specific genes.
XNAzymeA catalytic XNA molecule capable of cleaving RNA substrates, analogous to natural ribozymes but with enhanced stability due to the non-natural backbone.
AptamerA nucleic acid molecule that folds into a specific 3D shape to bind a target molecule with high affinity, functioning like an antibody. XNA aptamers have superior stability.
PolymeraseAn enzyme that synthesizes nucleic acid strands from a template. Engineered polymerases are required to replicate XNA, as natural polymerases cannot process non-natural backbones.
Nuclease ResistanceThe ability of a nucleic acid to resist degradation by nuclease enzymes, a critical property for therapeutic nucleic acids that must survive in the body.
Splice SwitchingA therapeutic mechanism where oligonucleotides bind to pre-mRNA splice sites to alter mRNA splicing patterns, restoring production of functional proteins in genetic diseases.
PhosphorothioateA chemical modification where one oxygen in the phosphodiester backbone is replaced with sulfur, conferring nuclease resistance and the most widely used modification in antisense oligonucleotide drugs.
siRNASmall interfering RNA, a class of double-stranded RNA molecules (20-25 nucleotides) that silence gene expression through the RNA interference pathway. Patisiran (Onpattro) was the first FDA-approved siRNA drug.
Gene SilencingThe process of reducing or eliminating the expression of a specific gene, achieved through antisense oligonucleotides, siRNA, or XNAzymes that target complementary mRNA sequences.
Orthogonal Genetic SystemA synthetic genetic system that operates independently of natural DNA/RNA, using XNA and engineered enzymes. Orthogonal systems enable biocontainment and novel biological functions without interfering with host genetics.
SELEXSystematic Evolution of Ligands by Exponential Enrichment, a laboratory technique for evolving aptamers and XNA molecules with specific binding or catalytic properties through iterative rounds of selection and amplification.
NucleotideThe basic building block of nucleic acids, consisting of a nitrogenous base, a sugar (or sugar analog in XNA), and a phosphate group (or analog). XNA nucleotides differ from natural ones in their sugar component.
BackboneThe repeating sugar-phosphate chain that forms the structural framework of nucleic acids. XNA is defined by having an alternative (non-natural) backbone while retaining base-pairing capability.
OligonucleotideA short nucleic acid polymer, typically 15-50 nucleotides long, used in therapeutics, diagnostics, and research. Most oligonucleotide drugs contain chemical modifications for stability.
RNase HA cellular enzyme that degrades the RNA strand of an RNA-DNA duplex. Antisense oligonucleotides that form duplexes with target mRNA can recruit RNase H to cleave and silence the target gene.
Melting Temperature (Tm)The temperature at which 50% of nucleic acid duplexes dissociate into single strands. Higher Tm indicates stronger base-pair binding. LNA modifications increase Tm by 2-8 degrees Celsius per nucleotide.
MiravirsenThe first LNA-based therapeutic to enter clinical trials, targeting microRNA-122 for hepatitis C treatment. It demonstrated the clinical viability of locked nucleic acid modifications in antisense drug design.
Nusinersen (Spinraza)An FDA-approved antisense oligonucleotide drug for spinal muscular atrophy that uses 2'-O-methoxyethyl modifications. It corrects SMN2 pre-mRNA splicing to produce functional SMN protein, transforming patient outcomes.