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        <secFileNumber>000-19125</secFileNumber>
        <issuerAddress>
          <com:street1>2855 GAZELLE COURT</com:street1>
          <com:city>CARLSBAD</com:city>
          <com:stateOrCountry>CA</com:stateOrCountry>
          <com:zipCode>92010</com:zipCode>
        </issuerAddress>
        <issuerContactPhone>7609319200</issuerContactPhone>
        <nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>O'NEIL PATRICK R.</nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>
        <relationshipsToIssuer>
          <relationshipToIssuer>Officer</relationshipToIssuer>
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        <securitiesClassTitle>Common Stock</securitiesClassTitle>
        <brokerOrMarketmakerDetails>
          <name>ETrade by Morgan Stanley</name>
          <address>
            <com:street1>200 Hudson Street, Suite 501</com:street1>
            <com:city>New Jersey</com:city>
            <com:stateOrCountry>NJ</com:stateOrCountry>
            <com:zipCode>07311</com:zipCode>
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        </brokerOrMarketmakerDetails>
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        <aggregateMarketValue>369000.00</aggregateMarketValue>
        <noOfUnitsOutstanding>142050000</noOfUnitsOutstanding>
        <approxSaleDate>01/18/2023</approxSaleDate>
        <securitiesExchangeName>NASDAQ</securitiesExchangeName>
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        <securitiesClassTitle>Common</securitiesClassTitle>
        <acquiredDate>01/17/2023</acquiredDate>
        <natureOfAcquisitionTransaction>RSUs granted under the 2011 Equity Incentive Plan</natureOfAcquisitionTransaction>
        <nameOfPersonfromWhomAcquired>Ionis Pharmaceuticals Inc</nameOfPersonfromWhomAcquired>
        <isGiftTransaction>N</isGiftTransaction>
        <amountOfSecuritiesAcquired>9000</amountOfSecuritiesAcquired>
        <paymentDate>01/18/2023</paymentDate>
        <natureOfPayment>Services rendered</natureOfPayment>
      </securitiesToBeSold>
      <nothingToReportFlagOnSecuritiesSoldInPast3Months>Y</nothingToReportFlagOnSecuritiesSoldInPast3Months>
      <noticeSignature>
        <noticeDate>01/18/2023</noticeDate>
        <signature>Patrick R. O'Neil</signature>
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text: 144
  0001564926
  XXXXXXXX
  LIVE
  0000874015
  IONIS PHARMACEUTICALS INC
  000-19125
  2855 GAZELLE COURT
  CARLSBAD
  CA
  92010
  7609319200
  O'NEIL PATRICK R.
  Officer
  Common Stock
  ETrade by Morgan Stanley
  200 Hudson Street, Suite 501
  New Jersey
  NJ
  07311
  9000
  369000.00
  142050000
  01/18/2023
  NASDAQ
  Common
  01/17/2023
  RSUs granted under the 2011 Equity Incentive Plan
  Ionis Pharmaceuticals Inc
  N
  9000
  01/18/2023
  Services rendered
  Y
  01/18/2023
  Patrick R. O'Neil