               SEQUENCE LISTING

<110> AlphaBeta AB

<120> Facilitated passage over the blood-brain barrier by co-administration of Bri2 BRICHOS domain and lipid microbubbles and/or nanodropplets


<130> 21117267

<160> 12

<170> BiSSAP 1.3.6

<210> 1
<211> 266
<212> PRT
<213> Homo sapiens


<400> 1
Met Val Lys Val Thr Phe Asn Ser Ala Leu Ala Gln Lys Glu Ala Lys 
1               5                   10                  15      
Lys Asp Glu Pro Lys Ser Gly Glu Glu Ala Leu Ile Ile Pro Pro Asp 
            20                  25                  30          
Ala Val Ala Val Asp Cys Lys Asp Pro Asp Asp Val Val Pro Val Gly 
        35                  40                  45              
Gln Arg Arg Ala Trp Cys Trp Cys Met Cys Phe Gly Leu Ala Phe Met 
    50                  55                  60                  
Leu Ala Gly Val Ile Leu Gly Gly Ala Tyr Leu Tyr Lys Tyr Phe Ala 
65                  70                  75                  80  
Leu Gln Pro Asp Asp Val Tyr Tyr Cys Gly Ile Lys Tyr Ile Lys Asp 
                85                  90                  95      
Asp Val Ile Leu Asn Glu Pro Ser Ala Asp Ala Pro Ala Ala Leu Tyr 
            100                 105                 110         
Gln Thr Ile Glu Glu Asn Ile Lys Ile Phe Glu Glu Glu Glu Val Glu 
        115                 120                 125             
Phe Ile Ser Val Pro Val Pro Glu Phe Ala Asp Ser Asp Pro Ala Asn 
    130                 135                 140                 
Ile Val His Asp Phe Asn Lys Lys Leu Thr Ala Tyr Leu Asp Leu Asn 
145                 150                 155                 160 
Leu Asp Lys Cys Tyr Val Ile Pro Leu Asn Thr Ser Ile Val Met Pro 
                165                 170                 175     
Pro Arg Asn Leu Leu Glu Leu Leu Ile Asn Ile Lys Ala Gly Thr Tyr 
            180                 185                 190         
Leu Pro Gln Ser Tyr Leu Ile His Glu His Met Val Ile Thr Asp Arg 
        195                 200                 205             
Ile Glu Asn Ile Asp His Leu Gly Phe Phe Ile Tyr Arg Leu Cys His 
    210                 215                 220                 
Asp Lys Glu Thr Tyr Lys Leu Gln Arg Arg Glu Thr Ile Lys Gly Ile 
225                 230                 235                 240 
Gln Lys Arg Glu Ala Ser Asn Cys Phe Ala Ile Arg His Phe Glu Asn 
                245                 250                 255     
Lys Phe Ala Val Glu Thr Leu Ile Cys Ser 
            260                 265     

<210> 2
<211> 119
<212> PRT
<213> Homo sapiens


<400> 2
Gln Thr Ile Glu Glu Asn Ile Lys Ile Phe Glu Glu Glu Glu Val Glu 
1               5                   10                  15      
Phe Ile Ser Val Pro Val Pro Glu Phe Ala Asp Ser Asp Pro Ala Asn 
            20                  25                  30          
Ile Val His Asp Phe Asn Lys Lys Leu Thr Ala Tyr Leu Asp Leu Asn 
        35                  40                  45              
Leu Asp Lys Cys Tyr Val Ile Pro Leu Asn Thr Ser Ile Val Met Pro 
    50                  55                  60                  
Pro Arg Asn Leu Leu Glu Leu Leu Ile Asn Ile Lys Ala Gly Thr Tyr 
65                  70                  75                  80  
Leu Pro Gln Ser Tyr Leu Ile His Glu His Met Val Ile Thr Asp Arg 
                85                  90                  95      
Ile Glu Asn Ile Asp His Leu Gly Phe Phe Ile Tyr Arg Leu Cys His 
            100                 105                 110         
Asp Lys Glu Thr Tyr Lys Leu 
        115                 

<210> 3
<211> 89
<212> PRT
<213> Homo sapiens


<400> 3
Met Val Lys Val Thr Phe Asn Ser Ala Leu Ala Gln Lys Glu Ala Lys 
1               5                   10                  15      
Lys Asp Glu Pro Lys Ser Gly Glu Glu Ala Leu Ile Ile Pro Pro Asp 
            20                  25                  30          
Ala Val Ala Val Asp Cys Lys Asp Pro Asp Asp Val Val Pro Val Gly 
        35                  40                  45              
Gln Arg Arg Ala Trp Cys Trp Cys Met Cys Phe Gly Leu Ala Phe Met 
    50                  55                  60                  
Leu Ala Gly Val Ile Leu Gly Gly Ala Tyr Leu Tyr Lys Tyr Phe Ala 
65                  70                  75                  80  
Leu Gln Pro Asp Asp Val Tyr Tyr Cys 
                85                  

<210> 4
<211> 23
<212> PRT
<213> Homo sapiens


<400> 4
Glu Ala Ser Asn Cys Phe Ala Ile Arg His Phe Glu Asn Lys Phe Ala 
1               5                   10                  15      
Val Glu Thr Leu Ile Cys Ser 
            20              

<210> 5
<211> 95
<212> PRT
<213> Homo sapiens


<400> 5
Phe Ala Asp Ser Asp Pro Ala Asn Ile Val His Asp Phe Asn Lys Lys 
1               5                   10                  15      
Leu Thr Ala Tyr Leu Asp Leu Asn Leu Asp Lys Cys Tyr Val Ile Pro 
            20                  25                  30          
Leu Asn Thr Ser Ile Val Met Pro Pro Arg Asn Leu Leu Glu Leu Leu 
        35                  40                  45              
Ile Asn Ile Lys Ala Gly Thr Tyr Leu Pro Gln Ser Tyr Leu Ile His 
    50                  55                  60                  
Glu His Met Val Ile Thr Asp Arg Ile Glu Asn Ile Asp His Leu Gly 
65                  70                  75                  80  
Phe Phe Ile Tyr Arg Leu Cys His Asp Lys Glu Thr Tyr Lys Leu 
                85                  90                  95  

<210> 6
<211> 95
<212> PRT
<213> Pan troglodytes


<400> 6
Phe Ala Asp Ser Asp Pro Ala Asn Ile Val His Asp Phe Asn Lys Lys 
1               5                   10                  15      
Leu Thr Ala Tyr Leu Asp Leu Asn Leu Asp Lys Cys Tyr Val Ile Pro 
            20                  25                  30          
Leu Asn Thr Ser Ile Val Met Pro Pro Arg Asn Leu Leu Glu Leu Leu 
        35                  40                  45              
Ile Asn Ile Lys Ala Gly Thr Tyr Leu Pro Gln Ser Tyr Leu Ile His 
    50                  55                  60                  
Glu His Met Val Ile Thr Asp Arg Ile Glu Asn Ile Asp His Leu Gly 
65                  70                  75                  80  
Phe Phe Ile Tyr Arg Leu Cys His Asp Lys Glu Thr Tyr Lys Leu 
                85                  90                  95  

<210> 7
<211> 95
<212> PRT
<213> Bos taurus


<400> 7
Phe Ala Asp Ser Asp Pro Ala Asn Ile Val His Asp Phe Asn Lys Lys 
1               5                   10                  15      
Leu Thr Ala Tyr Leu Asp Leu Asn Leu Asp Lys Cys Tyr Val Ile Pro 
            20                  25                  30          
Leu Asn Thr Ser Ile Val Met Pro Pro Lys Asn Leu Leu Glu Leu Leu 
        35                  40                  45              
Ile Asn Ile Lys Ala Gly Thr Tyr Leu Pro Gln Ser Tyr Leu Ile His 
    50                  55                  60                  
Glu His Met Val Ile Thr Asp Arg Ile Glu Asn Ile Asp His Leu Gly 
65                  70                  75                  80  
Phe Tyr Ile Tyr Arg Leu Cys His Asp Lys Glu Thr Tyr Lys Leu 
                85                  90                  95  

<210> 8
<211> 95
<212> PRT
<213> Sus scrofa


<400> 8
Phe Ala Asp Ser Asp Pro Ala Asn Ile Val His Asp Phe Asn Lys Lys 
1               5                   10                  15      
Leu Thr Ala Tyr Leu Asp Leu Asn Leu Asp Lys Cys Tyr Val Ile Pro 
            20                  25                  30          
Leu Asn Thr Ser Ile Val Met Pro Pro Arg Asn Leu Leu Glu Leu Leu 
        35                  40                  45              
Ile Asn Ile Lys Ala Gly Thr Tyr Leu Pro Gln Ser Tyr Leu Ile His 
    50                  55                  60                  
Glu His Met Val Ile Thr Asp Arg Ile Glu Asn Ile Asp His Leu Gly 
65                  70                  75                  80  
Phe Tyr Ile Tyr Arg Leu Cys His Asp Lys Glu Thr Tyr Lys Leu 
                85                  90                  95  

<210> 9
<211> 95
<212> PRT
<213> Mus musculus


<400> 9
Phe Ala Asp Ser Asp Pro Ala Asn Ile Val His Asp Phe Asn Lys Lys 
1               5                   10                  15      
Leu Thr Ala Tyr Leu Asp Leu Asn Leu Asp Lys Cys Tyr Val Ile Pro 
            20                  25                  30          
Leu Asn Thr Ser Ile Val Met Pro Pro Lys Asn Leu Leu Glu Leu Leu 
        35                  40                  45              
Ile Asn Ile Lys Ala Gly Thr Tyr Leu Pro Gln Ser Tyr Leu Ile His 
    50                  55                  60                  
Glu His Met Val Ile Thr Asp Arg Ile Glu Asn Val Asp Asn Leu Gly 
65                  70                  75                  80  
Phe Phe Ile Tyr Arg Leu Cys His Asp Lys Glu Thr Tyr Lys Leu 
                85                  90                  95  

<210> 10
<211> 95
<212> PRT
<213> Rattus norvegicus


<400> 10
Phe Ala Asp Ser Asp Pro Ala Asn Ile Val His Asp Phe Asn Lys Lys 
1               5                   10                  15      
Leu Thr Ala Tyr Leu Asp Leu Asn Leu Asp Lys Cys Tyr Val Ile Pro 
            20                  25                  30          
Leu Asn Thr Ser Ile Val Met Pro Pro Arg Asn Leu Leu Glu Leu Leu 
        35                  40                  45              
Ile Asn Ile Lys Ala Gly Thr Tyr Leu Pro Gln Ser Tyr Leu Ile His 
    50                  55                  60                  
Glu His Met Val Ile Thr Asp Arg Ile Glu Asn Val Asp His Leu Gly 
65                  70                  75                  80  
Phe Phe Ile Tyr Arg Leu Cys His Asp Lys Glu Thr Tyr Lys Leu 
                85                  90                  95  

<210> 11
<211> 127
<212> PRT
<213> Homo sapiens


<220> 
<221> DOMAIN
<222> 3..121
<223> Rh Bri2 BRICHOS domain

<220> 
<221> DOMAIN
<222> 122..127
<223> AU1 tag

<400> 11
Gly Ser Gln Thr Ile Glu Glu Asn Ile Lys Ile Phe Glu Glu Glu Glu 
1               5                   10                  15      
Val Glu Phe Ile Ser Val Pro Val Pro Glu Phe Ala Asp Ser Asp Pro 
            20                  25                  30          
Ala Asn Ile Val His Asp Phe Asn Lys Lys Leu Thr Ala Tyr Leu Asp 
        35                  40                  45              
Leu Asn Leu Asp Lys Cys Tyr Val Ile Pro Leu Asn Thr Ser Ile Val 
    50                  55                  60                  
Met Pro Pro Arg Asn Leu Leu Glu Leu Leu Ile Asn Ile Lys Ala Gly 
65                  70                  75                  80  
Thr Tyr Leu Pro Gln Ser Tyr Leu Ile His Glu His Met Val Ile Thr 
                85                  90                  95      
Asp Arg Ile Glu Asn Ile Asp His Leu Gly Phe Phe Ile Tyr Arg Leu 
            100                 105                 110         
Cys His Asp Lys Glu Thr Tyr Lys Leu Asp Thr Tyr Arg Tyr Ile 
        115                 120                 125         

<210> 12
<211> 363
<212> PRT
<213> Homo sapiens


<220> 
<221> DOMAIN
<222> 3..121
<223> Rh Bri2 BRICHOS domain

<220> 
<221> DOMAIN
<222> 129..363
<223> mCherry

<400> 12
Gly Ser Gln Thr Ile Glu Glu Asn Ile Lys Ile Phe Glu Glu Glu Glu 
1               5                   10                  15      
Val Glu Phe Ile Ser Val Pro Val Pro Glu Phe Ala Asp Ser Asp Pro 
            20                  25                  30          
Ala Asn Ile Val His Asp Phe Asn Lys Lys Leu Thr Ala Tyr Leu Asp 
        35                  40                  45              
Leu Asn Leu Asp Lys Cys Tyr Val Ile Pro Leu Asn Thr Ser Ile Val 
    50                  55                  60                  
Met Pro Pro Arg Asn Leu Leu Glu Leu Leu Ile Asn Ile Lys Ala Gly 
65                  70                  75                  80  
Thr Tyr Leu Pro Gln Ser Tyr Leu Ile His Glu His Met Val Ile Thr 
                85                  90                  95      
Asp Arg Ile Glu Asn Ile Asp His Leu Gly Phe Phe Ile Tyr Arg Leu 
            100                 105                 110         
Cys His Asp Lys Glu Thr Tyr Lys Leu Gly Gly Gly Gly Gly Gly Ser 
        115                 120                 125             
Val Ser Lys Gly Glu Glu Asp Asn Met Ala Ile Ile Lys Glu Phe Met 
    130                 135                 140                 
Arg Phe Lys Val His Met Glu Gly Ser Val Asn Gly His Glu Phe Glu 
145                 150                 155                 160 
Ile Glu Gly Glu Gly Glu Gly Arg Pro Tyr Glu Gly Thr Gln Thr Ala 
                165                 170                 175     
Lys Leu Lys Val Thr Lys Gly Gly Pro Leu Pro Phe Ala Trp Asp Ile 
            180                 185                 190         
Leu Ser Pro Gln Phe Met Tyr Gly Ser Lys Ala Tyr Val Lys His Pro 
        195                 200                 205             
Ala Asp Ile Pro Asp Tyr Leu Lys Leu Ser Phe Pro Glu Gly Phe Lys 
    210                 215                 220                 
Trp Glu Arg Val Met Asn Phe Glu Asp Gly Gly Val Val Thr Val Thr 
225                 230                 235                 240 
Gln Asp Ser Ser Leu Gln Asp Gly Glu Phe Ile Tyr Lys Val Lys Leu 
                245                 250                 255     
Arg Gly Thr Asn Phe Pro Ser Asp Gly Pro Val Met Gln Lys Lys Thr 
            260                 265                 270         
Met Gly Trp Glu Ala Ser Ser Glu Arg Met Tyr Pro Glu Asp Gly Ala 
        275                 280                 285             
Leu Lys Gly Glu Ile Lys Gln Arg Leu Lys Leu Lys Asp Gly Gly His 
    290                 295                 300                 
Tyr Asp Ala Glu Val Lys Thr Thr Tyr Lys Ala Lys Lys Pro Val Gln 
305                 310                 315                 320 
Leu Pro Gly Ala Tyr Asn Val Asn Ile Lys Leu Asp Ile Thr Ser His 
                325                 330                 335     
Asn Glu Asp Tyr Thr Ile Val Glu Gln Tyr Glu Arg Ala Glu Gly Arg 
            340                 345                 350         
His Ser Thr Gly Gly Met Asp Glu Leu Tyr Lys 
        355                 360             

