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<!-- DFIN ActiveDisclosure(SM) XBRL Schema Document - http://www.dfinsolutions.com/ -->
<!-- Creation Date      : 2020-07-27T16:03:18.5583191+00:00 -->
<!-- Version            : 5.0.1.476 -->
<!-- Package ID         : b988f55b313b4070beffb388949a7674 -->
<!-- Copyright (c) 2020 Donnelley Financial Solutions, Inc. All Rights Reserved. -->
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  <xsd:element id="crsp_IncreaseDecreaseInOperatingLeaseAssetsAndLiabilities" name="IncreaseDecreaseInOperatingLeaseAssetsAndLiabilities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="crsp_EquityIssuanceCostsInAccountsPayableAndAccruedExpenses" name="EquityIssuanceCostsInAccountsPayableAndAccruedExpenses" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="crsp_SummaryOfSignificantAccountingPoliciesLineItems" name="SummaryOfSignificantAccountingPoliciesLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_SummaryOfSignificantAccountingPoliciesTable" name="SummaryOfSignificantAccountingPoliciesTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_CasebiaTherapeuticsLlpMember" name="CasebiaTherapeuticsLlpMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_FurnitureFixturesAndOtherMember" name="FurnitureFixturesAndOtherMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_LaboratoryEquipmentMember" name="LaboratoryEquipmentMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_AccruedResearchAndDevelopmentExpenseCurrent" name="AccruedResearchAndDevelopmentExpenseCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_AccruedLicenseFeesCurrent" name="AccruedLicenseFeesCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_AccruedIntellectualPropertyCostsCurrent" name="AccruedIntellectualPropertyCostsCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_AccruedPropertyAndEquipment" name="AccruedPropertyAndEquipment" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_AnnualRentalPayment" name="AnnualRentalPayment" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_RentalPaymentsPeriodUnderLeaseArrangement" name="RentalPaymentsPeriodUnderLeaseArrangement" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="crsp_ContingenciesAndCommitmentsLineItems" name="ContingenciesAndCommitmentsLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_ContingenciesAndCommitmentsTable" name="ContingenciesAndCommitmentsTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_LeaseArrangementMember" name="LeaseArrangementMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_TwoThousandAndFifteenCollaborationAgreementMember" name="TwoThousandAndFifteenCollaborationAgreementMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_VertexPharmaceuticalsIncorporatedAndItsCertainSubsidiariesMember" name="VertexPharmaceuticalsIncorporatedAndItsCertainSubsidiariesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_LettersOfCreditIssued" name="LettersOfCreditIssued" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_MilestonePaymentReceivable" name="MilestonePaymentReceivable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="crsp_NonRefundableUpFrontPaymentReceived" name="NonRefundableUpFrontPaymentReceived" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_MaximumPotentialPayments" name="MaximumPotentialPayments" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="crsp_PercentageOfExchangePaymentOfResearchAndDevelopmentCosts" name="PercentageOfExchangePaymentOfResearchAndDevelopmentCosts" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="crsp_MyotonicDystrophyTypeOneRAndDServicesMember" name="MyotonicDystrophyTypeOneRAndDServicesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
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  <xsd:element id="crsp_CollaborativeArrangementMaterialRightsThreeMember" name="CollaborativeArrangementMaterialRightsThreeMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_CollaborativeArrangementMaterialRightsFourthExclusiveLicenseMember" name="CollaborativeArrangementMaterialRightsFourthExclusiveLicenseMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_CollaborativeArrangementMaterialRightsFourMember" name="CollaborativeArrangementMaterialRightsFourMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_BetaGlobinMember" name="BetaGlobinMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_NonExclusiveResearchLicenseMember" name="NonExclusiveResearchLicenseMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_RetirementAgreementMember" name="RetirementAgreementMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_TwoThousandAndNineteenOptionAgreementMember" name="TwoThousandAndNineteenOptionAgreementMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_CoCommercializationAgreementMember" name="CoCommercializationAgreementMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_CertainOptionsMember" name="CertainOptionsMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_TwoThousandAndNineteenCasebiaAgreementMember" name="TwoThousandAndNineteenCasebiaAgreementMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_ResearchAndDevelopmentServicesMember" name="ResearchAndDevelopmentServicesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_FutureDeliveryOfUpToTwoOptionsMember" name="FutureDeliveryOfUpToTwoOptionsMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_NumberOfOptionsWouldNotBeExercisedUnderAgreement" name="NumberOfOptionsWouldNotBeExercisedUnderAgreement" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="crsp_NumberOfRemainingOptionsUnderAgreement" name="NumberOfRemainingOptionsUnderAgreement" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="crsp_NonCashConsiderationReceived" name="NonCashConsiderationReceived" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_VariableConsiderationReceived" name="VariableConsiderationReceived" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_CollaborativeAndLicenseArrangementTransactionPrice" name="CollaborativeAndLicenseArrangementTransactionPrice" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_UpFrontPaymentReceived" name="UpFrontPaymentReceived" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_AgreementsDescription" name="AgreementsDescription" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="crsp_MilestonePaymentReceivableInclusiveOfExerciseOfEachExclusiveOption" name="MilestonePaymentReceivableInclusiveOfExerciseOfEachExclusiveOption" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="crsp_NumberOfExclusiveLicenseTargets" name="NumberOfExclusiveLicenseTargets" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="crsp_AggregateAmountInOptionExercisePaymentsReceivedUnderCollaborationAgreement" name="AggregateAmountInOptionExercisePaymentsReceivedUnderCollaborationAgreement" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="crsp_EstimatedStandaloneSellingPriceForSingleCollaboration" name="EstimatedStandaloneSellingPriceForSingleCollaboration" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_EstimatedStandaloneSellingPriceForCollaborationAgreement" name="EstimatedStandaloneSellingPriceForCollaborationAgreement" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_MaximumPotentialFuturePayments" name="MaximumPotentialFuturePayments" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_ResearchAndDevelopmentContractArrangementReimbursementsReceived" name="ResearchAndDevelopmentContractArrangementReimbursementsReceived" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_NumberOfOptionsExercisedUnderAgreement" name="NumberOfOptionsExercisedUnderAgreement" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="crsp_CollaborativeArrangementLicenseRightsReacquiredByWaivingPaymentOwed" name="CollaborativeArrangementLicenseRightsReacquiredByWaivingPaymentOwed" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_NonCashConsiderationExpensedUponExecutionOfCollaborativeAgreement" name="NonCashConsiderationExpensedUponExecutionOfCollaborativeAgreement" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
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  <xsd:element id="crsp_DateOfFormationOfJointVentureEntity" name="DateOfFormationOfJointVentureEntity" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="crsp_LimitedLiabilityCompanyLLCOrLimitedPartnershipLPOutstandingExchangeAmount" name="LimitedLiabilityCompanyLLCOrLimitedPartnershipLPOutstandingExchangeAmount" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
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  <xsd:element id="crsp_PercentageSharingOfProfitLossFromSaleOfProducts" name="PercentageSharingOfProfitLossFromSaleOfProducts" type="num:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" />
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  <xsd:element id="crsp_SalesAgreementWithJefferiesLLCMember" name="SalesAgreementWithJefferiesLLCMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_TwoThousandEighteenAtMarketOfferingMember" name="TwoThousandEighteenAtMarketOfferingMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_TwoThousandNineteenAtMarketOfferingMember" name="TwoThousandNineteenAtMarketOfferingMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_UnderwrittenPublicOfferingMember" name="UnderwrittenPublicOfferingMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_CommonStockRegisteredShareCapital" name="CommonStockRegisteredShareCapital" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" />
  <xsd:element id="crsp_CommonStockConditionalCapital" name="CommonStockConditionalCapital" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" />
  <xsd:element id="crsp_SwissLawMember" name="SwissLawMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_BondsOrSimilarDebtInstrumentsMember" name="BondsOrSimilarDebtInstrumentsMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_EmployeeBenefitPlansMember" name="EmployeeBenefitPlansMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_EstimatedGrossProceedsFromIssuanceOfCommonStock" name="EstimatedGrossProceedsFromIssuanceOfCommonStock" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_EquityIssuanceCosts" name="EquityIssuanceCosts" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="crsp_StockIssuanceCostAccruedCurrent" name="StockIssuanceCostAccruedCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="crsp_LossFromEquityMethodInvestmentsMember" name="LossFromEquityMethodInvestmentsMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_UnvestedRestrictedCommonSharesMember" name="UnvestedRestrictedCommonSharesMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="crsp_CollaborationAgreementMember" name="CollaborationAgreementMember" type="nonnum:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
</xsd:schema>
