Retargeted retroviral vectors resistant to vaccine-induced neutralization and compositions or methods of use thereof
AssigneesThe Broad Institute, Inc., The General Hospital Corporation
InventorsKepler MEARS, Robert MANGUSO, Kathleen YATES, Kyrellos IBRAHIM, Peter ALLEN
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Abstract
The invention features pseudotyped viral particles (e.g., lentiviral or gammaretroviral particles) and compositions and methods of use thereof, where the viral particles comprise a VHH domain.
Claims20
A pseudotyped viral particle comprising:
- (a) an envelope comprising a viral envelope glycoprotein domain or fragment thereof fused to a VHH domain or fragment thereof, wherein the VHH domain or fragment thereof specifically binds an antigen present on a target cell, and wherein the viral envelope glycoprotein comprises an alteration referenced to a measles virus glycoprotein at an amino acid targeted by a measles virus neutralizing antibody;
- and
- (b) a heterologous polynucleotide.
A method for delivering a heterologous polynucleotide to a target cell, the method comprising:
- contacting a target cell with a pseudotyped viral particle comprising:
- (a) an envelope comprising a viral envelope glycoprotein domain or fragment thereof fused to a VHH domain or fragment thereof, wherein the VHH domain or fragment thereof specifically binds an antigen present on the target cell, and wherein the viral envelope glycoprotein comprises an alteration referenced to a measles virus glycoprotein at an amino acid targeted by a measles virus neutralizing antibody;
- and
- (b) a heterologous polynucleotide,
- thereby delivering the heterologous polynucleotide to the target cell;
- or
- (a) an envelope comprising a viral envelope glycoprotein domain or fragment thereof fused to a VHH domain or fragment thereof, wherein the VHH domain or fragment thereof specifically binds an antigen present on the target cell, and wherein the viral envelope glycoprotein comprises an alteration referenced to a measles virus glycoprotein at an amino acid targeted by a measles virus neutralizing antibody;
- and
- (b) a heterologous polynucleotide,
- thereby delivering the heterologous polynucleotide to the subject.
A method of treating a subject having a cancer, the method comprising administering to the subject a composition comprising a pseudotyped viral particle, the pseudotyped viral particle comprising:
- (a) an envelope comprising a viral envelope glycoprotein domain or fragment thereof fused to a VHH domain or fragment thereof, wherein the VHH domain or fragment thereof specifically binds a tumor antigen present on a target cancer cell, and wherein the viral envelope glycoprotein comprises an alteration referenced to a measles virus glycoprotein at an amino acid targeted by a measles virus neutralizing antibody;
- and
- (b) a heterologous polynucleotide,
- thereby delivering the heterologous polynucleotide to the target cell in the subject and treating the subject.
A method for generating a pseudotyped viral particle for delivering a heterologous polynucleotide to a target cell, the method comprising:
- (a) displaying on the cell membrane of a eukaryotic cell a viral envelope glycoprotein domain or fragment thereof fused to a VHH domain or fragment thereof, wherein the VHH domain or fragment thereof specifically binds an antigen present on the target cell, and wherein the viral envelope glycoprotein comprises an alteration referenced to a measles virus glycoprotein at an amino acid targeted by a measles virus neutralizing antibody;
- (b) transfecting the eukaryotic cell with a viral transfer vector and one or more additional vectors encoding one or more viral polypeptides,
- thereby generating the pseudotyped viral particle for delivering a heterologous polynucleotide to the target cell.
A eukaryotic cell for generating a pseudotyped viral particle, the eukaryotic cell comprising:
- (a) a cell membrane comprising a viral envelope glycoprotein domain or fragment thereof fused to a VHH domain or fragment thereof, wherein the VHH domain or fragment thereof specifically binds an antigen present on a target cell, and wherein the viral envelope glycoprotein comprises an alteration referenced to a measles virus glycoprotein at an amino acid targeted by a measles virus neutralizing antibody;
- (b) a viral transfer vector;
- and
- (c) one or more additional vectors encoding one or more viral polypeptides.
A mammalian expression vector comprising a polynucleotide encoding a polypeptide comprising a viral envelope glycoprotein domain or fragment thereof fused to a VHH domain or fragment thereof, wherein the VHH domain or fragment thereof specifically binds an antigen present on a target cell, and wherein the viral envelope glycoprotein comprises an alteration referenced to a measles virus glycoprotein at an amino acid targeted by a measles virus neutralizing antibody.
A fusion protein suitable for pseudotyping a viral particle, wherein the fusion protein comprises a sequence with at least 85% sequence identity to a sequence selected from the group consisting of
- DMV-H-MHCII (N11)
- MSSPRDKVDAFYKDIPRPRNNRVLLDNERVIIERPLILVGVLAVMFLSLVGLLAIAGVRLQKAT
- TNSIEVNRKLSTNLETTVSIEHHVKDVLTPLFKIIGDEVGLRMPQKLTEIMQFISNKIKFLNPD
- REYDFNDLHWCVNPPDQVKIDYAQYCNHIAAEELIVTKFKELMNHSLDMSKGRIFPPKNCSGSV
- ITRGQTIKPGLTLVNIYTTRNFEVSFMVTVISGGMYGKTYFLKPPEPDDPFEFQAFRIFEVGLV
- RDVGSREPVLQMTNFMVIDEDEGLNFCLLSVGELRLAAVCVRGRPVVTKDIGGYKDEPFKVVTL
- GIIGGGLSNQKTEIYPTIDSSIEKLYITSHRGIIRNSKARWSVPAIRSDDKDKMEKCTQALCKS
- RPPPSCNSSDWEPLTSNRIPAYAYIALEIKEDSGLELDITSNYGPLIIHGAGMDIYEGPSSNQD
- WLAIPPLSQSVLGVINKVDFTAGFDIKPHTLTTAVDYESGKCYVPVELSGAKDQDLKLESNLVV
- LPTKDFGYVTATYDTSRSEHAIVYYVYDTARSSSYFFPFRIKARGEPIYLRIECFPWSRQLWCH
- HYCMINSTVSNEIVVVDNLVSINMSCSRGGGGSGGGGSGGGGSAAAQVQLVQSGGGLVQPGGSL
- GLSCAASGNIGSRDNMGWYRQAPGKQREWVATISGYGIATYRDSVKGRFTVAKDTAKNIVSLQM
- NYLTTEDTAVYYCYAYAVDSRNIFWSQGTQVTVS;
- DMV-H-CD7 (Humanized VHH10)
- MSSPRDKVDAFYKDIPRPRNNRVLLDNERVIIERPLILVGVLAVMFLSLVGLLAIAGVRLQKAT
- TNSIEVNRKLSTNLETTVSIEHHVKDVLTPLFKIIGDEVGLRMPQKLTEIMQFISNKIKFLNPD
- REYDFNDLHWCVNPPDQVKIDYAQYCNHIAAEELIVTKFKELMNHSLDMSKGRIFPPKNCSGSV
- ITRGQTIKPGLTLVNIYTTRNFEVSFMVTVISGGMYGKTYFLKPPEPDDPFEFQAFRIFEVGLV
- RDVGSREPVLQMTNFMVIDEDEGLNFCLLSVGELRLAAVCVRGRPVVTKDIGGYKDEPFKVVTL
- GIIGGGLSNQKTEIYPTIDSSIEKLYITSHRGIIRNSKARWSVPAIRSDDKDKMEKCTQALCKS
- RPPPSCNSSDWEPLTSNRIPAYAYIALEIKEDSGLELDITSNYGPLIIHGAGMDIYEGPSSNQD
- WLAIPPLSQSVLGVINKVDFTAGFDIKPHTLTTAVDYESGKCYVPVELSGAKDQDLKLESNLVV
- LPTKDFGYVTATYDTSRSEHAIVYYVYDTARSSSYFFPFRIKARGEPIYLRIECFPWSRQLWCH
- HYCMINSTVSNEIVVVDNLVSINMSCSRGGGGSGGGGSGGGGSAAADVQLQESGGGSVQAGGSL
- RLSCAASGYTHSSYCMAWFRQAPGREREGVASIDSDGTTSYADSVKGRFTISQDNAKNTLYLQM
- NSLKPEDTAMYYCAARFGPMGCVDLSTLSFGHWGQGTQVTVSITGGGSGGGSYPYDVPDYA;
- DMV-H-CD45 (32)
- MSSPRDKVDAFYKDIPRPRNNRVLLDNERVIIERPLILVGVLAVMFLSLVGLLAIAGVRLQKAT
- TNSIEVNRKLSTNLETTVSIEHHVKDVLTPLFKIIGDEVGLRMPQKLTEIMQFISNKIKFLNPD
- REYDFNDLHWCVNPPDQVKIDYAQYCNHIAAEELIVTKFKELMNHSLDMSKGRIFPPKNCSGSV
- ITRGQTIKPGLTLVNIYTTRNFEVSFMVTVISGGMYGKTYFLKPPEPDDPFEFQAFRIFEVGLV
- RDVGSREPVLQMTNFMVIDEDEGLNFCLLSVGELRLAAVCVRGRPVVTKDIGGYKDEPFKVVTL
- GIIGGGLSNQKTEIYPTIDSSIEKLYITSHRGIIRNSKARWSVPAIRSDDKDKMEKCTQALCKS
- RPPPSCNSSDWEPLTSNRIPAYAYIALEIKEDSGLELDITSNYGPLIIHGAGMDIYEGPSSNQD
- WLAIPPLSQSVLGVINKVDFTAGFDIKPHTLTTAVDYESGKCYVPVELSGAKDQDLKLESNLVV
- LPTKDFGYVTATYDTSRSEHAIVYYVYDTARSSSYFFPFRIKARGEPIYLRIECFPWSRQLWCH
- HYCMINSTVSNEIVVVDNLVSINMSCSRGGGGSGGGGSGGGGSAAAQVQLVQSGGGLVQPGGSL
- RLSCAASGRAFNSAAMGWYRQAPGSQRELVASISAGTASYADAVKGRFTISRDYAKNIIYLQMN
- SLKPDDTAVYFCNYRTTYTSGYSEDYWGQGTQVTVSGGGSGGGSYPYDVPDYA;
- CDV-H-MHCII (N11)
- MLPYQDKVGAFYKDNARANSTKLSLVTEGHGGRRPPYLLFVLLILLVGILALLAITGVRFHQVS
- TSNMEFSRLLKEDMEKSEAVHHQVIDVLTPLFKIIGDEIGLRLPQKLNEIKQFILQKTNFFNPN
- REFDFRDLHWCINPPSTVKVNFTNYCESIGIRKAIASAANPILLSALSGGRGDIFPPHRCSGAT
- TSVGKVFPLSVSLSMSLISRTSEVINMLTAISDGVYGKTYLLVPDDIEREFDTREIRVFEIGFI
- KRWLNDMPLLQTTNYMVLPKNSKAKVCTIAVGELTLASLCVEESTVLLYHDSSGSQDGILVVTL
- GIFWATPMDHIEEVIPVAHPSMKKIHITNHRGFIKDSIATWMVPALASEKQEEQKGCLESACQR
- KTYPMCNQASWEPFGGRQLPSYGRLTLPLDASVDLQLNISFTYGPVILNGDGMDYYESPLLNSG
- WLTIPPKDGTISGLINKAGRGDQFTVLPHVLTFAPRESSGNCYLPIQTSQIRDRDVLIESNIVV
- LPTQSIRYVIATYDISRSDHAIVYYVYDPIRTISYTHPFRLTTKGRPDFLRIECFVWDDNLWCH
- QFYRFEADIANSTTSVENLVRIRFSCNRGGGGSGGGGSGGGGSAAAQVQLVQSGGGLVQPGGSL
- GLSCAASGNIGSRDNMGWYRQAPGKQREWVATISGYGIATYRDSVKGRFTVAKDTAKNIVSLQM
- NYLTTEDTAVYYCYAYAVDSRNIFWSQGTQVTVSGGGSGGGSYPYDVPDYA;
- CDV-H-CD7 (Humanized VHH10)
- MLPYQDKVGAFYKDNARANSTKLSLVTEGHGGRRPPYLLFVLLILLVGILALLAITGVRFHQVS
- TSNMEFSRLLKEDMEKSEAVHHQVIDVLTPLFKIIGDEIGLRLPQKLNEIKQFILQKTNFFNPN
- REFDFRDLHWCINPPSTVKVNFTNYCESIGIRKAIASAANPILLSALSGGRGDIFPPHRCSGAT
- TSVGKVFPLSVSLSMSLISRTSEVINMLTAISDGVYGKTYLLVPDDIEREFDTREIRVFEIGFI
- KRWLNDMPLLQTTNYMVLPKNSKAKVCTIAVGELTLASLCVEESTVLLYHDSSGSQDGILVVTL
- GIFWATPMDHIEEVIPVAHPSMKKIHITNHRGFIKDSIATWMVPALASEKQEEQKGCLESACQR
- KTYPMCNQASWEPFGGRQLPSYGRLTLPLDASVDLQLNISFTYGPVILNGDGMDYYESPLLNSG
- WLTIPPKDGTISGLINKAGRGDQFTVLPHVLTFAPRESSGNCYLPIQTSQIRDRDVLIESNIVV
- LPTQSIRYVIATYDISRSDHAIVYYVYDPIRTISYTHPFRLTTKGRPDFLRIECFVWDDNLWCH
- QFYRFEADIANSTTSVENLVRIRFSCNRGGGGSGGGGSGGGGSAAADVQLQESGGGSVQAGGSL
- RLSCAASGYTHSSYCMAWFRQAPGREREGVASIDSDGTTSYADSVKGRFTISQDNAKNTLYLQM
- NSLKPEDTAMYYCAARFGPMGCVDLSTLSFGHWGQGTQVTVSITGGGSGGGSYPYDVPDYA;
- CDV-H-CD45 VHH (32)
- MLPYQDKVGAFYKDNARANSTKLSLVTEGHGGRRPPYLLFVLLILLVGILALLAITGVRFHQVS
- TSNMEFSRLLKEDMEKSEAVHHQVIDVLTPLFKIIGDEIGLRLPQKLNEIKQFILQKTNFFNPN
- REFDFRDLHWCINPPSTVKVNFTNYCESIGIRKAIASAANPILLSALSGGRGDIFPPHRCSGAT
- TSVGKVFPLSVSLSMSLISRTSEVINMLTAISDGVYGKTYLLVPDDIEREFDTREIRVFEIGFI
- KRWLNDMPLLQTTNYMVLPKNSKAKVCTIAVGELTLASLCVEESTVLLYHDSSGSQDGILVVTL
- GIFWATPMDHIEEVIPVAHPSMKKIHITNHRGFIKDSIATWMVPALASEKQEEQKGCLESACQR
- KTYPMCNQASWEPFGGRQLPSYGRLTLPLDASVDLQLNISFTYGPVILNGDGMDYYESPLLNSG
- WLTIPPKDGTISGLINKAGRGDQFTVLPHVLTFAPRESSGNCYLPIQTSQIRDRDVLIESNIVV
- LPTQSIRYVIATYDISRSDHAIVYYVYDPIRTISYTHPFRLTTKGRPDFLRIECFVWDDNLWCH
- QFYRFEADIANSTTSVENLVRIRFSCNRGGGGSGGGGSGGGGSAAAQVQLVQSGGGLVQPGGSL
- RLSCAASGRAFNSAAMGWYRQAPGSQRELVASISAGTASYADAVKGRFTISRDYAKNIIYLQMN
- SLKPDDTAVYFCNYRTTYTSGYSEDYWGQGTQVTVSAAAYPYDVPDYA;
- MeV-Hc18-CDV-MHCII (N11)
- MGSRIVINREHLMIDRPYVLLAVLFVMFLSLIGLLAIAGIRLHRAAIYTAEIHKSLSTNLDVTN
- SIEHQVKDVLTPLFKIIGDEVGLRTPQRFTDLVKFISDKIKFLNPDREYDFRDLTWCINPPERI
- KLDYDQYCADVAARKAIASAANPILLSALSGGRGDIFPPHRCSGATTSVGKVFPLSVSLSMSLI
- SRTSEVINMLTAISDGVYGKTYLLVPDDIEREFDTREIRVFEIGFIKRWLNDMPLLQTTNYMVL
- PKNSKAKVCTIAVGELTLASLCVEESTVLLYHDSSGSQDGILVVTLGIFWATPMDHIEEVIPVA
- HPSMKKIHITNHRGFIKDSIATWMVPALASEKQEEQKGCLESACQRKTYPMCNQASWEPFGGRQ
- LPSYGRLTLPLDASVDLQLNISFTYGPVILNGDGMDYYESPLLNSGWLTIPPKDGTISGLINKA
- GRGDQFTVLPHVLTFAPRESSGNCYLPIQTSQIRDRDVLIESNIVVLPTQSIRYVIATYDISRS
- DHAIVYYVYDPIRTISYTHPFRLTTKGRPDFLRIECFVWDDNLWCHQFYRFEADIANSTTSVEN
- LVRIRFSCNRGGGGSGGGGSGGGGSAAAQVQLVQSGGGLVQPGGSLGLSCAASGNIGSRDNMGW
- YRQAPGKQREWVATISGYGIATYRDSVKGRFTVAKDTAKNIVSLQMNYLTTEDTAVYYCYAYAV
- DSRNIFWSQGTQVTVSGGGSGGGSYPYDVPDYA;
- MeV-Hc18-DMV-MHCII (N11)
- MGSRIVINREHLMIDRPYVLLAVLFVMFLSLIGLLAIAGIRLHRAAIYTAEIHKSLSTNLDVTN
- SIEHQVKDVLTPLFKIIGDEVGLRTPQRFTDLVKFISDKIKFLNPDREYDERDLTWCINPPERI
- KLDYDQYCADVAAEELIVTKFKELMNHSLDMSKGRIFPPKNCSGSVITRGQTIKPGLTLVNIYT
- TRNFEVSFMVTVISGGMYGKTYFLKPPEPDDPFEFQAFRIFEVGLVRDVGSREPVLQMTNFMVI
- DEDEGLNFCLLSVGELRLAAVCVRGRPVVTKDIGGYKDEPFKVVTLGIIGGGLSNQKTEIYPTI
- DSSIEKLYITSHRGIIRNSKARWSVPAIRSDDKDKMEKCTQALCKSRPPPSCNSSDWEPLTSNR
- IPAYAYIALEIKEDSGLELDITSNYGPLIIHGAGMDIYEGPSSNQDWLAIPPLSQSVLGVINKV
- DFTAGFDIKPHTLTTAVDYESGKCYVPVELSGAKDQDLKLESNLVVLPTKDFGYVTATYDTSRS
- EHAIVYYVYDTARSSSYFFPFRIKARGEPIYLRIECFPWSRQLWCHHYCMINSTVSNEIVVVDN
- LVSINMSCSRGGGGSGGGGSGGGGSAAAQVQLVQSGGGLVQPGGSLGLSCAASGNIGSRDNMGW
- YRQAPGKQREWVATISGYGIATYRDSVKGRFTVAKDTAKNIVSLQMNYLTTEDTAVYYCYAYAV
- DSRNIFWSQGTQVTVSGGGSGGGSYPYDVPDYA;
- FMV-H-CD45 (32) polypeptide
- MESNNIKYYKDSSRYFGKILDEHKTINSQLYSLSIKVITIIAIIVSLIATIITIINATSGRTTL
- NSNTDILLSQRDEIHNIQEMIFDRIYPLINAMSTELGLHIPTLLDELTKAIDQKIKIMHPPVDT
- VTSDLNWCIKPPNGIIIDPKSYCESMELSKTYELLLDQLDVSRKKSLIINRKNINQCQLVDNSK
- IIFATVNIQSTPRFLNFGHTVSNQRITFGQGTYSSTYVITIQEDGVTDVQYRVFEIGYISDQFG
- VFPSLIVSRVLPIRMLLGMESCTLTSDRLGGYFLCMNTLTRSIYDYVSIRDLKSLYITIPHYGK
- VNYTYFNFGKIRSPHEIDKIWLTSDRGQIISGYFAAFVTITIRNYNNYPYKCLNNPCFDNSENY
- CRGWYKNITGTDDVPILAYLLVEMYDEEGPLITLVAIPPYNYTAPSHNSLYYDDKINKLIMTTS
- HIGYIQINEVHEVIVGDNLKAILLNRLSDEHPNLTACRLNQGIKEQYKSDGTIISNSALIDIQE
- RMYITVKAIPPAGNYNFTVELHSRSNTSYVSLPKQFNAKYDKLHLECFSWDKSWWCALIPQFSL
- SWNESLSVDTAIFNLISCKGGGGSGGGGSGGGGSAAAQVQLVQSGGGLVQPGGSLRLSCAASGR
- AFNSAAMGWYRQAPGSQRELVASISAGTASYADAVKGRFTISRDYAKNIIYLQMNSLKPDDTAV
- YFCNYRTTYTSGYSEDYWGQGTQVTVSGGGSGGGSYPYDVPDYA;
- PPRV-H-CD45 (32)
- MSAQRERINAFYKDNLHNKTHRVILDRERLTIERPYILLGVLLVMFLSLIGLLAIAGIRLHRAT
- VGTAEIQSRLNTNIELTESIDHQTKDVLTPLFKIIGDEVGIRIPQKFSDLVKFISDKIKFLNPD
- REYDFRDLRWCMNPPERVKINFDQFCEYKAAVKSVEHIFESSLNRSERLRLLTLGPGTGCLGRT
- VTRAQFSELTLTLMDLDLEIKHNVSSVFTVVEEGLFGRTYTVWRSDTGKPSTSPGIGHFLRVFE
- IGLVRDLELGAPIFHMTNYLTVNMSDDYRSCLLAVGELKLTALCTPSETVTLSESGVPKREPLV
- VVILNLAGPTLGGELYSVLPTTDPTVEKLYLSSHRGIIKDNEANWVVPSTDVRDLQNKGECLVE
- ACKTRPPSFCNGTGIGPWSEGRIPAYGVIRVSLDLASDPGVVITSVFGPLIPHLSGMDLYNNPF
- SRAAWLAVPPYEQSFLGMINTIGFPDRAEVMPHILTTEIRGPRGRCHVPIELSSRIDDDIKIGS
- NMVVLPTKDLRYITATYDVSRSEHAIVYYIYDTGRSSSYFYPVRLNFRGNPLSLRIECFPWYHK
- VWCYHDCLIYNTITNEEVHTRGLTGIEVTCNPVGGGGSGGGGSGGGGSAAAQVQLVQSGGGLVQ
- PGGSLRLSCAASGRAFNSAAMGWYRQAPGSQRELVASISAGTASYADAVKGRFTISRDYAKNII
- YLQMNSLKPDDTAVYFCNYRTTYTSGYSEDYWGQGTQVTVSGGGSGGGSYPYDVPDYA;
- RPV-H-CD45 (32)
- MSPPRDRVDAYYKDNFQFKNTRVVLNKEQLLIERPCMLLTVLFVMFLSLVGLLAIAGIRLHRAA
- VNTAKINNDLTTSIDITKSIEYQVKDVLTPLFKIIGDEVGLRTPQRFTDLTKFISDKIKFLNPD
- KEYDFRDINWCINPPERIKIDYDQYCAHTAAEDLITMLVNSSLTGTTVLRTSLVNLGRNCTGPT
- TTKGQFSNISLTLSGIYSGRGYNISSMITITGKGMYGSTYLVGKYNQRARRPSIVWQQDYRVFE
- VGIIRELGVGTPVFHMTNYLELPRQPELETCMLALGESKLAALCLADSPVALHYGRVGDDNKIR
- FVKLGVWASPADRDTLATLSAIDPTLDGLYITTHRGIIAAGTAIWAVPVTRTDDQVKMGKCRLE
- ACRDRPPPFCNSTDWEPLEAGRIPAYGVLTIKLGLADEPKVDIISEFGPLITHDSGMDLYTSFD
- GTKYWLTTPPLQNSALGTVNTLVLEPSLKISPNILTLPIRSGGGDCYTPTYLSDRADDDVKLSS
- NLVILPSRDLQYVSATYDISRVEHAIVYHIYSTGRLSSYYYPFKLPIKGDPVSLQIECFPWDRK
- LWCHHFCSVIDSGTGEQVTHIGVVGIEITCNGKGGGGSGGGGSGGGGSAAAQVQLVQSGGGLVQ
- PGGSLRLSCAASGRAFNSAAMGWYRQAPGSQRELVASISAGTASYADAVKGRFTISRDYAKNII
- YLQMNSLKPDDTAVYFCNYRTTYTSGYSEDYWGQGTQVTVSGGGSGGGSYPYDVPDYA;
- and
- RMV-H-CD45 (32)
- MSAQRERINAFYKDNPHNKNHRVILDRERLVIERPYILLGVLLVMFLSLIGLLAIAGIRLHRAT
- VGTSEIQSRLNTNIELTESIDHQTKDVLTPLFKIIGDEVGIRIPQKFSDLVKFISDKIKFLNPD
- REYDFRDLRWCMNPPERVKINFDQFCEYKAAVKSIEHIFESPLNKSKKLQSLTLGPGTGCLGRT
- VTRAHFSELTLTLMDLDLEMKHNVSSVFTVVEEGLFGRTYTVWRSDARDPSTDLGIGHFLRVFE
- IGLVRDLGLGPPVFHMTNYLTVNMSDDYRRCLLAVGELKLTALCSSSETVTLGERGVPKREPLV
- VVILNLAGPTLGGELYSVLPTSDLMVEKLYLSSHRGIIKDDEANWVVPSTDVRDLQNKGECLVE
- ACKTRPPSFCNGTGSGPWSEGRIPAYGVIRVSLDLASDPGVVITSVFGPLIPHLSGMDLYNNPF
- SRAVWLAVPPYEQSFLGMINTIGFPNRAEVMPHILTTEIRGPRGRCHVPIELSRRVDDDIKIGS
- NMVILPTIDLRYITATYDVSRSEHAIVYYIYDTGRSSSYFYPVRLNFKGNPLSLRIECFPWRHK
- VWCYHDCLIYNTITDEEVHTRGLTGIEVTCNPVGGGGSGGGGSGGGGSAAAQVQLVQSGGGLVQ
- PGGSLRLSCAASGRAFNSAAMGWYRQAPGSQRELVASISAGTASYADAVKGRFTISRDYAKNII
- YLQMNSLKPDDTAVYFCNYRTTYTSGYSEDYWGQGTQVTVSGGGSGGGSYPYDVPDYA.
A chimeric viral envelope glycoprotein polypeptide or fragment thereof suitable for pseudotyping a viral particle comprising an amino acid sequence at least about 20 amino acids in length derived from a non-measles virus morbillivirus F protein extravirion domain N-terminal to an amino acid sequence at least about 20 amino acids in length derived from a measles virus F protein extravirion, wherein the chimeric viral envelope glycoprotein polypeptide comprises the amino acid sequence RLDVGTNLGNAIAKLEDAKELLESSDQILRSMKGLSSTS (MeV-F extravirion stalk domain), wherein the non-measles virus morbillivirus is selected from the group consisting of canine distemper virus, dolphin Morbillivirus, feline Morbillivirus, measles virus, Peste des petits ruminant virus, phocine Morbillivirus, Rinderpest virus, and small ruminant virus, and wherein the chimeric protein comprises a sequence with at least 85% sequence identity to a sequence selected from the group consisting of
- F2 DMV Fusion
- MAASNGGVMYQSFLTIIILVIMTEGQIHWGNLSKIGIVGTGSASYKVMTRPNHQYLVIKLMPNV
- TMIDNCTRTEVTEYRKLLKTVLEPVKNALTVITKNIKPIQSLYPYDVPDYATTSRRSKRFAGVV
- LAGAALGVATAAQITAGIALHQSMLNSQAIDNLRASLETTNQAIEAIRQAGQEMILAVQGVQDY
- INNELIPSMNQLSCDLIGQKLGLKLLRYYTEILSLFGPSLRDPISAEISIQALSYALGGDINKV
- LEKLGYSGGDLLGILESRGIKARITHVDTESYFIVLSIAYPTLSEIKGVIVHRLEGVSYNIGSQ
- EWYTTVPKYVATQGYLISNFDESSCTFMPEGTVCSQNALYPMSPLLQECLRGSTKSCARTLVSG
- SFGNRFILSQGNLIANCASILCKCYTTGTIINQDPDKILTYIAADHCPVVEVNGVTIQVGSRRY
- PDAVYLHRIDLGPPISLERLDVGTNLGNAIAKLEDAKELLESSDQILRSMKGLSSTSIVYILIA
- VCLGGLIGIPALICCCRGR;
- S-SDMV Fusion
- MAASNGGVMYQSFLTIIILVIMTEGQIHWGNLSKIGIVGTGSASYKVMTRPNHQYLVIKLMPNV
- TMIDNCTRTEVTEYRKLLKTVLEPVKNALTVITKNIKPIQSLYPYDVPDYATTSRRSKRFAGVV
- LAGVALGVATAAQITAGVALHQSIMNSQSIDNLRTSLEKSNQAIEEIRQASQETVLAVQGVQDF
- INNELIPSMHQLSCEMLGQKLGLKLLRYYTEILSIFGPSLRDPISAEISIQALSYALGGDINKV
- LEKLGYSGGDLLGILESRGIKARITHVDTESYFIVLSIAYPTLSEIKGVIVHRLEGVSYNIGSQ
- EWYTTVPKYVATQGYLISNFDESSCTFMPEGTVCSQNALYPMSPLLQECLRGSTKSCARTLVSG
- SFGNRFILSQGNLIANCASILCKCYTTGTIINQDPDKILTYIAADHCPVVEVNGVTIQVGSRRY
- PDAVYLHRIDLGPPISLERLDVGTNLGNAIAKLEDAKELLESSDQILRSMKGLSSTSSIVYILI
- AVCLGGLIGIPALICCCRGR;
- Intermediate DMV Fusion
- MAASNGGVMYQSFLTIIILVIMTEGQIHWGNLSKIGIVGTGSASYKVMTRPNHQYLVIKLMPNV
- TMIDNCTRTEVTEYRKLLKTVLEPVKNALTVITKNIKPIQSLYPYDVPDYATTSRRSKRFAGVV
- LAGVALGVATAAQITAGVALHQSIMNSQSIDNLRTSLEKSNQAIEEIRQASQETVLAVQGVQDF
- INNELIPSMHQLSCEMLGQKLGLKLLRYYTEILSIFGPSLRDPVSAEISIQALSYALGGDINKI
- LEKLGYSGADLLAILESRGIKAKVTHVDLEGYFIVLSIAYPTLSEVKGVIVHKLEGVSYNIGSQ
- EWYTTVPKYVATQGYLISNFDESSCTFMPEGTVCSQNALYPMSPLLQECLRGSTKSCARTLVSG
- SFGNRFILSQGNLIANCASILCKCYTTGTIINQDPDKILTYIAADHCPVVEVNGVTIQVGSRRY
- PDAVYLHRIDLGPPISLERLDVGTNLGNAIAKLEDAKELLESSDQILRSMKGLSSTSSIVYILI
- AVCLGGLIGIPALICCCRGR;
- H Interacting Domain DMV Fusion
- MAASNGGVMYQSFLTIIILVIMTEGQIHWGNLSKIGIVGTGSASYKVMTRPNHQYLVIKLMPNV
- TMIDNCTRTEVTEYRKLLKTVLEPVKNALTVITKNIKPIQSLYPYDVPDYATTSRRSKRFAGVV
- LAGVALGVATAAQITAGVALHQSIMNSQSIDNLRTSLEKSNQAIEEIRQASQETVLAVQGVQDF
- INNELIPSMHQLSCEMLGQKLGLKLLRYYTEILSIFGPSLRDPVSAEISIQALSYALGGDINKI
- LEKLGYSGADLLAILESRGIKAKVTHVDLEGYFIVLSIAYPTLSEVKGVIVHKLEAVSYNLGSQ
- EWYTTLPKYVATNGYLISNFDESSCAFMSEVTICSQNALYPMSPLLQQCLRGSTASCARSLVSG
- TIGNRFILSKGNLIANCASVLCKCYTTGTIINQDPDKILTYIAADHCPVVEVNGVTIQVGSRRY
- PDAVYLHRIDLGPPISLERLDVGTNLGNAIAKLEDAKELLESSDQILRSMKGLSSTSSIVYILI
- AVCLGGLIGIPALICCCRGR;
- and
- Stalk DMV Fusion
- MAASNGGVMYQSFLTIIILVIMTEGQIHWGNLSKIGIVGTGSASYKVMTRPNHQYLVIKLMPNV
- TMIDNCTRTEVTEYRKLLKTVLEPVKNALTVITKNIKPIQSLYPYDVPDYATTSRRSKRFAGVV
- LAGVALGVATAAQITAGVALHQSIMNSQSIDNLRTSLEKSNQAIEEIRQASQETVLAVQGVQDF
- INNELIPSMHQLSCEMLGQKLGLKLLRYYTEILSIFGPSLRDPVSAEISIQALSYALGGDINKI
- LEKLGYSGADLLAILESRGIKAKVTHVDLEGYFIVLSIAYPTLSEVKGVIVHKLEAVSYNLGSQ
- EWYTTLPKYVATNGYLISNFDESSCAFMSEVTICSQNALYPMSPLLQQCLRGSTASCARSLVSG
- TIGNRFILSKGNLIANCASVLCKCYSTGTIISQDPDKLLTFVAADKCPLVEVDGITIQVGSREY
- PDSVYVSRIDLGPAISLERLDVGTNLGNAIAKLEDAKELLESSDQILRSMKGLSSTSSIVYILI
- AVCLGGLIGIPALICCCRGR.
Dependencies are inferred from the claim text.