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<!-- DFIN ActiveDisclosure(SM) XBRL Schema Document - http://www.dfinsolutions.com/ -->
<!-- Creation Date      : 2021-11-03T15:27:33.3709118+00:00 -->
<!-- Version            : 5.0.1.702 -->
<!-- Package ID         : f428305c8a474b8e829d3cdcc73ad2c6 -->
<!-- Copyright (c) 2021 Donnelley Financial Solutions, Inc. All Rights Reserved. -->
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  <xsd:element id="ortx_StockIssuedDuringPeriodValueExerciseOfShareOptionsAndEmployeeStockPurchasePlan" name="StockIssuedDuringPeriodValueExerciseOfShareOptionsAndEmployeeStockPurchasePlan" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_StockIssuedDuringPeriodSharesAsPartOfCollaborationAgreement" name="StockIssuedDuringPeriodSharesAsPartOfCollaborationAgreement" type="xbrli:sharesItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_StockIssuedDuringPeriodValueAsPartOfCollaborationAgreement" name="StockIssuedDuringPeriodValueAsPartOfCollaborationAgreement" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_PrepaidExpensesAndOtherCurrentAssetsTextBlock" name="PrepaidExpensesAndOtherCurrentAssetsTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_LicenseAgreementsDisclosureTextBlock" name="LicenseAgreementsDisclosureTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_LicenseAgreementsAbstract" name="LicenseAgreementsAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_CollaborativeArrangementAbstract" name="CollaborativeArrangementAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_ResearchAndDevelopmentIncomeTaxCreditsPolicyTextBlock" name="ResearchAndDevelopmentIncomeTaxCreditsPolicyTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_ResearchAgreementCostAndAccrualPolicy" name="ResearchAgreementCostAndAccrualPolicy" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_StrimvelisLossProvisionPolicyTextBlock" name="StrimvelisLossProvisionPolicyTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_ScheduleOfChangesInLossProvisionTableTextBlock" name="ScheduleOfChangesInLossProvisionTableTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_ScheduleOfIntangibleAssetsNetOfAccumulatedAmortizationTableTextBlock" name="ScheduleOfIntangibleAssetsNetOfAccumulatedAmortizationTableTextBlock" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_ClosingPriceOfShareDate" name="ClosingPriceOfShareDate" type="xbrli:dateItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_PaymentsOfOtherIssuanceCosts" name="PaymentsOfOtherIssuanceCosts" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_NetProceedsFromIssuanceOfPrivatePlacement" name="NetProceedsFromIssuanceOfPrivatePlacement" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_OrganizationConsolidationAndPresentationOfFinancialStatementsLineItems" name="OrganizationConsolidationAndPresentationOfFinancialStatementsLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_OrganizationConsolidationAndPresentationOfFinancialStatementsTable" name="OrganizationConsolidationAndPresentationOfFinancialStatementsTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_SecuritiesPurchaseAgreementMember" name="SecuritiesPurchaseAgreementMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_SummaryOfSignificantAccountingPoliciesAbstract" name="SummaryOfSignificantAccountingPoliciesAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_SummaryOfSignificantAccountingPoliciesLineItems" name="SummaryOfSignificantAccountingPoliciesLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_SummaryOfSignificantAccountingPoliciesTable" name="SummaryOfSignificantAccountingPoliciesTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_FremontLeaseAgreementMember" name="FremontLeaseAgreementMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_ResearchAndDevelopmentTaxCreditReceivable" name="ResearchAndDevelopmentTaxCreditReceivable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_IncreaseDecreaseInEscrowDeposit" name="IncreaseDecreaseInEscrowDeposit" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_IncreaseDecreaseInAssetAcquisitionLiabilityEffectOfForeignExchangeTranslation" name="IncreaseDecreaseInAssetAcquisitionLiabilityEffectOfForeignExchangeTranslation" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_AssetAcquisitionLiabilityAssumed" name="AssetAcquisitionLiabilityAssumed" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_AssetAcquisitionLiabilityAssumedCurrent" name="AssetAcquisitionLiabilityAssumedCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_AssetAcquisitionLiabilityAssumedNonCurrent" name="AssetAcquisitionLiabilityAssumedNonCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_CashEquivalentsAbstract" name="CashEquivalentsAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsAmortizedCost" name="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsAmortizedCost" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_PrepaidExternalResearchAndDevelopmentExpenses" name="PrepaidExternalResearchAndDevelopmentExpenses" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_ConstructionDepositsCurrent" name="ConstructionDepositsCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_LabEquipmentMember" name="LabEquipmentMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_ImpairmentOfConstructionInProcess" name="ImpairmentOfConstructionInProcess" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_ImpairmentOfLaboratoryEquipment" name="ImpairmentOfLaboratoryEquipment" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_OtherNonCurrentAssets" name="OtherNonCurrentAssets" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_ConstructionDepositsLongTerm" name="ConstructionDepositsLongTerm" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_AccruedExternalResearchAndDevelopmentExpensesCurrent" name="AccruedExternalResearchAndDevelopmentExpensesCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_AccruedMilestonePaymentsCurrent" name="AccruedMilestonePaymentsCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_TheFirstTrancheTermLoanMember" name="TheFirstTrancheTermLoanMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_TheSecondTrancheTermLoanMember" name="TheSecondTrancheTermLoanMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_TheThirdTrancheTermLoanMember" name="TheThirdTrancheTermLoanMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_LondonInterbankOfferedRateFloorMember" name="LondonInterbankOfferedRateFloorMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_TermLoanMember" name="TermLoanMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_LineOfCreditFacilityInterestPaymentsTerm" name="LineOfCreditFacilityInterestPaymentsTerm" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_LineOfCreditFacilityAmortizationTerm" name="LineOfCreditFacilityAmortizationTerm" type="xbrli:durationItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_LineOfCreditFacilityPercentageOfFinalPayment" name="LineOfCreditFacilityPercentageOfFinalPayment" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_LineOfCreditFacilityCovenantsMinimumCashAllowed" name="LineOfCreditFacilityCovenantsMinimumCashAllowed" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_LongTermDebtBeforeAccretionIssuanceCostsNet" name="LongTermDebtBeforeAccretionIssuanceCostsNet" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_LongTermDebtBeforeAccretionIssuanceCostsNetCurrent" name="LongTermDebtBeforeAccretionIssuanceCostsNetCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_LongTermDebtBeforeAccretionIssuanceCostsNetNoncurrent" name="LongTermDebtBeforeAccretionIssuanceCostsNetNoncurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_AccretionRelatedToFinalPayment" name="AccretionRelatedToFinalPayment" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_TwoThousandAndEighteenShareOptionAndIncentivePlanMember" name="TwoThousandAndEighteenShareOptionAndIncentivePlanMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_TwoThousandAndEighteenEmployeeSharePurchasePlanMember" name="TwoThousandAndEighteenEmployeeSharePurchasePlanMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_TwoThousandAndTwentyInducementEquityPlanMember" name="TwoThousandAndTwentyInducementEquityPlanMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_TimeBasedRestrictedShareUnitsMember" name="TimeBasedRestrictedShareUnitsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_MenloParkCaliforniaMember" name="MenloParkCaliforniaMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_FremontCaliforniaMember" name="FremontCaliforniaMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_OperatingLeaseRightOfUseAssetFairValue" name="OperatingLeaseRightOfUseAssetFairValue" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_NumberOfAdditionalProgramsInPreclinicalDevelopment" name="NumberOfAdditionalProgramsInPreclinicalDevelopment" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_NumberOfLateStageClinicalGeneTherapyPrograms" name="NumberOfLateStageClinicalGeneTherapyPrograms" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_NumberOfEarlierStageClinicalGeneTherapyProgram" name="NumberOfEarlierStageClinicalGeneTherapyProgram" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_NumberOfAdditionalEarlierStageDevelopmentPrograms" name="NumberOfAdditionalEarlierStageDevelopmentPrograms" type="xbrli:integerItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_GSKAssetPurchaseAndLicenseAgreementMember" name="GSKAssetPurchaseAndLicenseAgreementMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_TelethonOSRLicenseAgreementsMember" name="TelethonOSRLicenseAgreementsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_OxfordBioMedicaLicenseDevelopmentAndSupplyAgreementMember" name="OxfordBioMedicaLicenseDevelopmentAndSupplyAgreementMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_PaymentOfTieredRoyaltyMaximumPercentage" name="PaymentOfTieredRoyaltyMaximumPercentage" type="dtr-types:percentItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" />
  <xsd:element id="ortx_MilestonePaymentsPayableUponAchievementOfCertainSalesMilestones" name="MilestonePaymentsPayableUponAchievementOfCertainSalesMilestones" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_UpfrontAndMilestonePayments" name="UpfrontAndMilestonePayments" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_InProcessResearchAndDevelopmentExpenseForUpfrontAndMilestonePayments" name="InProcessResearchAndDevelopmentExpenseForUpfrontAndMilestonePayments" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_UpfrontPaymentDescription" name="UpfrontPaymentDescription" type="xbrli:stringItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" />
  <xsd:element id="ortx_MilestonePayment" name="MilestonePayment" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_MilestonePaymentsReceivable" name="MilestonePaymentsReceivable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_StrategicCollaborationAgreementWithPharmingMember" name="StrategicCollaborationAgreementWithPharmingMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_SharePurchaseAgreementWithPharmingMember" name="SharePurchaseAgreementWithPharmingMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_PharmingAgreementsMember" name="PharmingAgreementsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_ProceedsFromPremiumSharesIssued" name="ProceedsFromPremiumSharesIssued" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_ProceedsFromUpfrontPayment" name="ProceedsFromUpfrontPayment" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_ProceedsFromUpfrontPaymentsAttributedToEquitySold" name="ProceedsFromUpfrontPaymentsAttributedToEquitySold" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_ProceedsFromUpfrontPaymentsAttributedToResearchActivities" name="ProceedsFromUpfrontPaymentsAttributedToResearchActivities" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_ExcessProceedsFromFairValueOfSharesIssuedAllocatedToCollaborationAgreement" name="ExcessProceedsFromFairValueOfSharesIssuedAllocatedToCollaborationAgreement" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="debit" />
  <xsd:element id="ortx_ProceedsFromNonRefundableUpfrontPayment" name="ProceedsFromNonRefundableUpfrontPayment" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_ReimbursementRevenueMember" name="ReimbursementRevenueMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_UpfrontAndMilestonePaymentRevenueMember" name="UpfrontAndMilestonePaymentRevenueMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_ManufacturingCommitmentsAmountDueInRemainderOfFiscalYear" name="ManufacturingCommitmentsAmountDueInRemainderOfFiscalYear" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_ManufacturingCommitmentsAmountDueInNextTwelveMonths" name="ManufacturingCommitmentsAmountDueInNextTwelveMonths" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_ManufacturingCommitmentsAmountDueInYearTwo" name="ManufacturingCommitmentsAmountDueInYearTwo" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_ManufacturingCommitmentsAmountDueInYearThree" name="ManufacturingCommitmentsAmountDueInYearThree" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_ManufacturingCommitmentsAmountDueInYearFour" name="ManufacturingCommitmentsAmountDueInYearFour" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_ManufacturingCommitments" name="ManufacturingCommitments" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_ProductManufacturingCommitmentsMember" name="ProductManufacturingCommitmentsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_DedicatedManufacturingAndDevelopmentResourcesMember" name="DedicatedManufacturingAndDevelopmentResourcesMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_ExclusiveTransductionSuitesMember" name="ExclusiveTransductionSuitesMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
  <xsd:element id="ortx_AccruedExpensesRelatedPartyCurrent" name="AccruedExpensesRelatedPartyCurrent" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" nillable="true" abstract="false" xbrli:balance="credit" />
  <xsd:element id="ortx_GSKMember" name="GSKMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" nillable="true" abstract="true" />
</xsd:schema>
