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  <xsd:element abstract="true" id="phio_CollaborativeArrangementClinicalCodevelopmentAgreementMember" name="CollaborativeArrangementClinicalCodevelopmentAgreementMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_CommonStockOutstandingMember" name="CommonStockOutstandingMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
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  <xsd:element abstract="true" id="phio_DocumentAndEntityInformation" name="DocumentAndEntityInformation" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_EmployeeRelatedResearchExpensesMember" name="EmployeeRelatedResearchExpensesMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element id="phio_EquityIssuableMaximumValue" name="EquityIssuableMaximumValue" nillable="true" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType" xbrli:balance="credit" xbrli:periodType="instant"/>
  <xsd:element abstract="true" id="phio_ExistingWarantsMember" name="ExistingWarantsMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_ExistingWarrantsDecember2024Member" name="ExistingWarrantsDecember2024Member" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_ExistingWarrantsJanuary2025Member" name="ExistingWarrantsJanuary2025Member" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_ExistingWarrantsJuly2025Member" name="ExistingWarrantsJuly2025Member" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_FormerCorporateHeadquartersMember" name="FormerCorporateHeadquartersMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_GeneralAndAdministrativeMember" name="GeneralAndAdministrativeMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_HcWainwrightCoLlcMember" name="HcWainwrightCoLlcMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_January132025OfferingsMember" name="January132025OfferingsMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_January142025OfferingsMember" name="January142025OfferingsMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_January162025OfferingsMember" name="January162025OfferingsMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_July2025FinancingMember" name="July2025FinancingMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_LaboratoryFacilityWorcesterMassachusettsMember" name="LaboratoryFacilityWorcesterMassachusettsMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element id="phio_LiquidityPolicyTextBlock" name="LiquidityPolicyTextBlock" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_NewWarrantsJuly2025Member" name="NewWarrantsJuly2025Member" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_NewWarrantsNovember2025Member" name="NewWarrantsNovember2025Member" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_NoteToFinancialStatementDetailsTextual" name="NoteToFinancialStatementDetailsTextual" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_NotesToFinancialStatements" name="NotesToFinancialStatements" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_NotesToFinancialStatementsAbstract" name="NotesToFinancialStatementsAbstract" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_November2025FinancingMember" name="November2025FinancingMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element id="phio_NumberOfWarrantsPerUnit" name="NumberOfWarrantsPerUnit" nillable="true" substitutionGroup="xbrli:item" type="xbrli:sharesItemType" xbrli:periodType="instant"/>
  <xsd:element id="phio_OperatingLeasesMonthlyPayment" name="OperatingLeasesMonthlyPayment" nillable="true" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType" xbrli:balance="credit" xbrli:periodType="duration"/>
  <xsd:element id="phio_PaymentsForAccruedObligationsOnCollaborativeArrangements" name="PaymentsForAccruedObligationsOnCollaborativeArrangements" nillable="true" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType" xbrli:balance="credit" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_PlacementAgentWarrantsMember" name="PlacementAgentWarrantsMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_PlacementAgentWarrantsOneMember" name="PlacementAgentWarrantsOneMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_PlacementAgentWarrantsThreeMember" name="PlacementAgentWarrantsThreeMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_PlacementAgentWarrantsTwoMember" name="PlacementAgentWarrantsTwoMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_PolicyTable" name="PolicyTable" nillable="true" substitutionGroup="xbrldt:hypercubeItem" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element id="phio_ProceedsFromIssuanceOfCommonStockAndWarrants" name="ProceedsFromIssuanceOfCommonStockAndWarrants" nillable="true" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType" xbrli:balance="debit" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_RegisteredDirectOfferingMember" name="RegisteredDirectOfferingMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_ReportableSegmentMember" name="ReportableSegmentMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element id="phio_ResearchAndDevelopmentAccruals" name="ResearchAndDevelopmentAccruals" nillable="true" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType" xbrli:balance="credit" xbrli:periodType="instant"/>
  <xsd:element abstract="true" id="phio_ResearchAndDevelopmentMember" name="ResearchAndDevelopmentMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_ResearchOfPh762Member" name="ResearchOfPh762Member" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_ResearchOfPh894Member" name="ResearchOfPh894Member" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_SeriesAWarrantsMember" name="SeriesAWarrantsMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_SeriesGWarrantsMember" name="SeriesGWarrantsMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_SeriesHWarrantsMember" name="SeriesHWarrantsMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_SeriesIWarrantsMember" name="SeriesIWarrantsMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_SeriesJWarrantsMember" name="SeriesJWarrantsMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_SeriesKWarrantsMember" name="SeriesKWarrantsMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element id="phio_StockIssuedDuringPeriodSharesStocksAndWarrants" name="StockIssuedDuringPeriodSharesStocksAndWarrants" nillable="true" substitutionGroup="xbrli:item" type="xbrli:sharesItemType" xbrli:periodType="duration"/>
  <xsd:element id="phio_StockIssuedDuringPeriodSharesWarrantsExercised" name="StockIssuedDuringPeriodSharesWarrantsExercised" nillable="true" substitutionGroup="xbrli:item" type="xbrli:sharesItemType" xbrli:periodType="duration"/>
  <xsd:element id="phio_StockIssuedDuringPeriodValueStocksAndWarrants" name="StockIssuedDuringPeriodValueStocksAndWarrants" nillable="true" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType" xbrli:balance="credit" xbrli:periodType="duration"/>
  <xsd:element id="phio_StockIssuedDuringPeriodValueWarrantsExercised" name="StockIssuedDuringPeriodValueWarrantsExercised" nillable="true" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType" xbrli:balance="credit" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_The2020PlanMember" name="The2020PlanMember" nillable="true" substitutionGroup="xbrli:item" type="dtr-types:domainItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_statement-statement-note-2-accounts-payable-and-accrued-liabilities-schedule-of-accrued-expenses-details" name="statement-statement-note-2-accounts-payable-and-accrued-liabilities-schedule-of-accrued-expenses-details" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_statement-statement-note-2-accounts-payable-and-accrued-liabilities-tables" name="statement-statement-note-2-accounts-payable-and-accrued-liabilities-tables" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_statement-statement-note-5-stockholders-equity-schedule-of-outstanding-warrants-details" name="statement-statement-note-5-stockholders-equity-schedule-of-outstanding-warrants-details" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_statement-statement-note-5-stockholders-equity-tables" name="statement-statement-note-5-stockholders-equity-tables" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_statement-statement-note-6-stockbased-compensation-restricted-stock-units-activity-details" name="statement-statement-note-6-stockbased-compensation-restricted-stock-units-activity-details" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_statement-statement-note-6-stockbased-compensation-tables" name="statement-statement-note-6-stockbased-compensation-tables" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_statement-statement-note-6-stockbased-compensation-total-stockbased-compensation-expense-details" name="statement-statement-note-6-stockbased-compensation-total-stockbased-compensation-expense-details" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_statement-statement-note-7-net-loss-per-common-share-schedule-of-antidilutive-securities-details" name="statement-statement-note-7-net-loss-per-common-share-schedule-of-antidilutive-securities-details" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_statement-statement-note-7-net-loss-per-common-share-tables" name="statement-statement-note-7-net-loss-per-common-share-tables" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_statement-statement-note-8-segment-information-schedule-of-segment-reporting-information-details" name="statement-statement-note-8-segment-information-schedule-of-segment-reporting-information-details" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_statement-statement-note-8-segment-information-tables" name="statement-statement-note-8-segment-information-tables" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
  <xsd:element abstract="true" id="phio_statement-statement-significant-accounting-policies-policies" name="statement-statement-significant-accounting-policies-policies" nillable="true" substitutionGroup="xbrli:item" type="xbrli:stringItemType" xbrli:periodType="duration"/>
</xsd:schema>
