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  <xs:element name="BicycleCollaborationMember" id="ions_BicycleCollaborationMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="AccruedCommercialExpensesCurrent" id="ions_AccruedCommercialExpensesCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" />
  <xs:element name="AccruedClinicalDevelopmentExpenses" id="ions_AccruedClinicalDevelopmentExpenses" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" />
  <xs:element name="AccruedInLicensingFeesCurrent" id="ions_AccruedInLicensingFeesCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="instant" xbrli:balance="credit" />
  <xs:element name="PropertyPlantAndEquipmentExcludingLandMember" id="ions_PropertyPlantAndEquipmentExcludingLandMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="BiogenCollaboration2013StrategicNeurologyMember" id="ions_BiogenCollaboration2013StrategicNeurologyMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="OtherMember" id="ions_OtherMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="OtsukaCollaborationDonidalorsenMember" id="ions_OtsukaCollaborationDonidalorsenMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="ResearchAndDevelopmentServicesForDonidalorsenMember" id="ions_ResearchAndDevelopmentServicesForDonidalorsenMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="LicenseOfDonidalorsenMember" id="ions_LicenseOfDonidalorsenMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="IonisOperationsMember" id="ions_IonisOperationsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" abstract="true" xbrli:periodType="duration" />
  <xs:element name="DrugDiscoveryExpenses" id="ions_DrugDiscoveryExpenses" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
  <xs:element name="DrugDevelopmentExpenses" id="ions_DrugDevelopmentExpenses" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
  <xs:element name="MedicalAffairsExpenses" id="ions_MedicalAffairsExpenses" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
  <xs:element name="ManufacturingAndDevelopmentChemistryExpenses" id="ions_ManufacturingAndDevelopmentChemistryExpenses" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
  <xs:element name="ResearchAndDevelopmentSupportExpenses" id="ions_ResearchAndDevelopmentSupportExpenses" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" abstract="false" xbrli:periodType="duration" xbrli:balance="debit" />
</xs:schema>
