Improved reverse transcriptase and methods of use

Abstract

Described are polymerases, e.g., a reverse transcriptase, e.g., MarathonRT or UltraMarathonRT, variants thereof, and fragments of variants thereof which have improved functional properties, e.g., stability, yield, or enzyme activity, and methods of use thereof.

Description

IMPROVED REVERSE TRANSCRIPTASE AND METHODS OF USECROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 63 / 665,792, filed June 28, 2024. The disclosure of each of the foregoing applications is incorporated herein by reference in its entirety.REFERENCE TO SEQUENCE LISTING SUBMITTED ELECTRONICALLY

[0002] This application contains a Sequence Listing, which is submitted electronically via EFS-Web as an XML Document formatted sequence listing with a file name “047162-5385- 00WO Sequence Listing.xml,” having a creation date of June 26, 2025, and having a size of 88,562 bytes. The sequence listing submitted via EFS-Web is part of the specification and is herein incorporated by reference in its entirety.BACKGROUND

[0003] Reverse transcriptases are polymerase enzymes capable of synthesizing a DNA polynucleotide in a sequence-directed manner using a template RNA polynucleotide. The commercial utility of reverse transcriptases is limited by their stability, yield during purification, and enzyme activity. Thus, there is a need to identify variants of reverse transcriptases capable of increased stability, yield, and / or enzyme activity.SUMMARY

[0004] The present disclosure features polymerases, e.g., DNA polymerases, e.g., reverse transcriptases with improved properties. These properties may comprise improved stability, yield, and / or enzyme activity. The polymerases, e.g., reverse transcriptases, described herein comprise fragments or variants of polymerases, e.g., reverse transcriptases, capable of reverse transcriptase activity and / or template switching activity. The polymerase, e.g., reverse transcriptase, as well as a fragment or variant thereof, e.g., described herein, may be capable of improved stability, yield, and / or enzyme activity, e.g., reverse transcriptase activity or template switching activity. The polymerase (or a fragment or variant described herein) may have reversetranscriptase activity. In some embodiments, the reverse transcriptase is a group II intron- encoded reverse transcriptase. In some embodiments, the reverse transcriptase is a thermostable group II intron reverse transcriptase. In one aspect, the present disclosure provides a reverse transcriptase, wherein the reverse transcriptase comprises a mutation relative to a reference sequence in at least one of the following domains: (i) the reverse transcriptase (RT) domain (e.g., finger subdomain (e.g., the RTO motif) or the palm subdomain (e.g., the insertion in the finger domain (IFD) motif)); and / or (ii) the thumb domain (e.g., the DNA binding domain (DBD)). In some embodiments, the mutation is a positively charged, negatively charged, or neutral mutation. In some embodiments, the mutation is at an arginine residue. In some embodiments, the mutation is at a lysine residue.

[0005] In some embodiments, the polymerase, e.g., reverse transcriptase, described herein comprises a sequence, e.g., an amino acid sequence, e.g., relative to a reference sequence. In some embodiments, the reference sequence comprises the amino acid sequence of a reverse transcriptase, e.g., a group II intron reverse transcriptase. The reference sequence may comprise the amino acid sequence of a group II intron reverse transcriptase encoded by a bacterium. The reference sequence may comprise the amino acid sequence of a group II intron reverse transcriptase encoded by a thermophilic bacterium, e.g., Eubacterium rectale, Roseburia intestinalis, Thermosynechococcus elongatus, or Geobacillus stearothermophilus, or a fragment or variant thereof. The reference sequence may comprise the amino acid sequence of a reverse transcriptase, e.g., a group II intron reverse transcriptase, e.g., a MarathonRT, UltraMarathonRT, TGIRT, or Induro RT reverse transcriptase, or a fragment or variant thereof. In some embodiments, the reference sequence comprises the amino acid sequence of a group II intron reverse transcriptase. In some embodiments, the reference sequence comprises the amino acid sequence of a MarathonRT reverse transcriptase. In some embodiments, the reference sequence comprises the amino acid sequence of an UltraMarathonRT reverse transcriptase.

[0006] In some embodiments, the mutation is within an alpha helix, a beta sheet, or a loop within the polymerase, e.g., the reference transcriptase. In some embodiments, the mutation is within an alpha helix, e.g., a7, alO, al l, al3, al5, or al6 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within a beta sheet, e.g., 6 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within a loop, e.g., L4, LI 5, L20, L22, or L23 of areference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from amino acid position 58, 59, 160, 240, 243, 247, 266, 289, 303, 338, 342, 347, 349, 351, 358, 361, 381, 382, 388, 389, or 396, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from amino acid position 58, 59, 160, 240, 243, 247, 266, 282, 289, 293, 303, 308, 338, 342, 347, 349, 351, 358, 361, 381, 382, 388, 389, or 396, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R58X, K59X, R160X, R240X, R243X, R247X, R266X, K289X, K303X, K338X, K342X, R347X, R349X, R351X, K358X, K361X, R381X, R382X, K388X, R389X, and K396X, wherein X is any amino acid, , e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R58X, K59X, R160X, R240X, R243X, R247X, R266X, R282X, K289X, K293X, K303X, R308X, K338X, K342X, R347X, R349X, R351X, K358X, K361X, R381X, R382X, K388X, R389X, and K396X, wherein X is any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R58Q, R58K, K59S, K59T, K59N, K59Q, K59D, K59E, K59A, R160S, R160T, R160N, R160Q, R160D, R160E, R160A, R240S, R240T, R240N, R240Q, R240D, R240E, R240A, R243S, R243T, R243N, R243Q, R243D, R243E, R243A, R247S, R247T, R247N, R247Q, R247D, R247E, R247A, R266S, R266T, R266N, R266Q, R266D, R266E, R266A, K289S, K289T, K289N, K289Q, K289D, K289E, K289A, K3O3S, K303T, K3O3N, K303Q, K303D, K303E, K303A, K338S, K338T, K338N, K338Q, K338D, K338E, K338A, K342S, K342T, K342N, K342Q, K342D, K342E, K342A, R347S, R347T, R347N, R347Q, R347D, R347E, R347A, R349T, R349Q, R349E, R349A, R351T, R351Q, R351N, R351D, R351E, R351S, R351A, K358S, K358T, K358N, K358Q, K358D, K358E, K358A, K361S, K361T, K361N, K361Q, K361D, K361E, K361A, R381T, R381Q, R381N, R382S, R382T, R382N, R382Q, R382D, R382E, R382A, K388S, K388T, K388N, K388Q, K388D, K388E, K388A, R389S, R389T, R389N, R389Q, R389D, R389E, R389A, K396S, K396T, K396N, K396Q, K396D, K396E, and K396A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R58Q, R58K, K59S, K59T, K59N, K59Q, K59D, K59E, K59A, R160S, R160T, R160N,R160Q, R160D, R160E, R160A, R240S, R240T, R240N, R240Q, R240D, R240E, R240A, R243S, R243T, R243N, R243Q, R243D, R243E, R243A, R247S, R247T, R247N, R247Q, R247D, R247E, R247A, R266S, R266T, R266N, R266Q, R266D, R266E, R266A, R282E, R282D, R282S, R282T, R282N, R282Q, R282A, K289S, K289T, K289N, K289Q, K289D, K289E, K289A, K293Q, K293R, K293H, K293D, K293E, K293N, K293S, K293T, K293A, K303S, K303T, K303N, K303Q, K303D, K303E, K303A, R308E, R308D, R308N, R308Q, R308S, R308T, R308A, K338S, K338T, K338N, K338Q, K338D, K338E, K338A, K342S, K342T, K342N, K342Q, K342D, K342E, K342A, R347S, R347T, R347N, R347Q, R347D, R347E, R347A, R349T, R349Q, R349E, R349A, R351T, R351Q, R351N, R351D, R351E, R351S, R351A, K358S, K358T, K358N, K358Q, K358D, K358E, K358A, K361S, K361T, K361N, K361Q, K361D, K361E, K361A, R381T, R381Q, R381N, R382S, R382T, R382N, R382Q, R382D, R382E, R382A, K388S, K388T, K388N, K388Q, K388D, K388E, K388A, R389S, R389T, R389N, R389Q, R389D, R389E, R389A, K396S, K396T, K396N, K396Q, K396D, K396E, and K396A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0007] In some embodiments, the mutation is in the RT domain of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within an alpha helix, e.g., a7 or alO of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within a beta sheet, e.g., P6 of a reference sequence described herein, e g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within a loop, e.g., L4 or LI 5 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within a loop, e.g., L4, L15, or L16 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from any of amino acid positions 1-290 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from amino acid position 58, 59, 160, 240, 243, 247, 266, and 289 wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from amino acid position 58, 59, 160, 240, 243, 247, 266, 282, and 289 wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R58X, K59X, R160X,R240X, R243X, R247X, R266X, and K289X, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R58X, K59X, R160X, R240X, R243X, R247X, R266X, R282X, and K289X, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R58Q, R58K, K59S, K59T, K59N, K59Q, K59D, K59E, K59A, R160S, R160T, R160N, R160Q, R160D, R160E, R160A, R240S, R240T, R240N, R240Q, R240D, R240E, R240A, R243S, R243T, R243N, R243Q, R243D, R243E, R243A, R247S, R247T, R247N, R247Q, R247D, R247E, R247A, R266S, R266T, R266N, R266Q, R266D, R266E, R266A, K289S, K289T, K289N, K289Q, K289D, K289E, and K289A, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R58Q, R58K, K59S, K59T, K59N, K59Q, K59D, K59E, K59A, R160S, R160T, R160N, R160Q, R160D, R160E, R160A, R240S, R240T, R240N, R240Q, R240D, R240E, R240A, R243S, R243T, R243N, R243Q, R243D, R243E, R243A, R247S, R247T, R247N, R247Q, R247D, R247E, R247A, R266S, R266T, R266N, R266Q, R266D, R266E, R266A, R282E, R282D, R282S, R282T, R282N, R282Q, R282A, K289S, K289T, K289N, K289Q, K289D, K289E, and K289A, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0008] In some embodiments, the mutation is in the finger subdomain of a reference sequence described herein, e g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within a loop, e.g., L4 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from any of amino acid positions 1-82, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from amino acid position 58 and 59, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R58X and K59X, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from: R58Q, R58K,K59S, K59T, K59N, K59Q, K59D, K59E, and K59A, e.g., relative to SEQ ID NO: 1 or SEQ IDNO: 2.

[0009] In some embodiments, the mutation is in the RTO motif of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within a loop, e.g., L4 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from any of amino acid positions 5-59, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from amino acid position 58 and 59, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R58X and K59X, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R58Q, R58K, K59S, K59T, K59N, K59Q, K59D, K59E, and K59A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0010] In some embodiments, the mutation is in the palm subdomain of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within an alpha helix, e.g., a7 or alO of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within a loop, e.g., L15 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within a loop, e.g., L15 or L16 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within a beta sheet, e.g., 06 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from any of amino acid positions 83-290, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from amino acid position 160, 240, 243, 247, 266, and 289, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from amino acid position 160, 240, 243,247, 266, 282, and 289, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R160X, R240X, R243X, R247X, R266X, and K289X, wherein X is any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R160X, R240X, R243X, R247X, R266X, R282X, and K289X, wherein X is any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R160S, R160T, R160N, R160Q, R160D, R160E, R160A, R240S, R240T, R240N, R240Q, R240D, R240E, R240A, R243S, R243T, R243N, R243Q, R243D, R243E, R243A, R247S, R247T, R247N, R247Q, R247D, R247E, R247A, R266S, R266T, R266N, R266Q, R266D, R266E, R266A, K289S, K289T, K289N, K289Q, K289D, K289E, and K289A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R160S, R160T, R160N, R160Q, R160D, R160E, R160A, R240S, R240T, R240N, R240Q, R240D, R240E, R240A, R243S, R243T, R243N, R243Q, R243D, R243E, R243A, R247S, R247T, R247N, R247Q, R247D, R247E, R247A, R266S, R266T, R266N, R266Q, R266D, R266E, R266A, R282E, R282D, R282S, R282T, R282N, R282Q, R282A, K289S, K289T, K289N, K289Q, K289D, K289E, and K289A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0011] In some embodiments, the mutation is in the insertion in the finger domain (IFD) motif of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within an alpha helix, e.g., a7 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from any of amino acid positions 151-176, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises amino acid position 160, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is R160X, wherein X is any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from R160S, R160T, R160N, R160Q, R160D, R160E, and R160A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0012] In some embodiments, the insertion is in the thumb domain of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within an alpha helix, e.g., all, a!3, al5, or al6 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within a loop, e.g., L20, L22, or L23 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within a loop, e.g., L18, L20, L22, or L23 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from any of amino acid positions 291-427, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from amino acid position 303, 338, 342, 347, 349, 351, 358, 361, 381, 382, 388, 389, and 396, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from amino acid position 293, 303, 308, 338, 342, 347, 349, 351, 358, 361, 381, 382, 388, 389, and 396, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from K303X, K338X, K342X, R347X, R349X, R351X, K358X, K361X, R381X, R382X, K388X, R389X, and K396X, wherein X is any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from K293X, K3O3X, R308X, K338X, K342X, R347X, R349X, R351X, K358X, K361X, R381X, R382X, K388X, R389X, and K396X, wherein X is any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from K303S, K303T, K303N, K303Q, K303D, K3O3E, K303A, K338S, K338T, K338N, K338Q, K338D, K338E, K338A, K342S, K342T, K342N, K342Q, K342D, K342E, K342A, R347S, R347T, R347N, R347Q, R347D, R347E, R347A, R349T, R349Q, R349E, R349A, R351T, R351Q, R351N, R351D, R351E, R351S, R351A, K358S, K358T, K358N, K358Q, K358D, K358E, K358A, K361S, K361T, K361N, K361Q, K361D, K361E, K361A, R381T, R381Q, R381N, R382S, R382T, R382N, R382Q, R382D, R382E, R382A, K388S, K388T, K388N, K388Q, K388D, K388E, K388A, R389S, R389T, R389N, R389Q, R389D, R389E, R389A, K396S,K396T, K396N, K396Q, K396D, K396E, and K396A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from K293Q, K293R, K293H, K293D, K293E, K293N, K293S, K293T, K293A, K303S, K303T, K303N, K303Q, K303D, K303E, R308E, R308D, R308N, R308Q, R308S, R308T, R308A, K303A, K338S, K338T, K338N, K338Q, K338D, K338E, K338A, K342S, K342T, K342N, K342Q, K342D, K342E, K342A, R347S, R347T, R347N, R347Q, R347D, R347E, R347A, R349T, R349Q, R349E, R349A, R351T, R351Q, R351N, R351D, R351E, R351S, R351A, K358S, K358T, K358N, K358Q, K358D, K358E, K358A, K361S, K361T, K361N, K361Q, K361D, K361E, K361A, R381T, R381Q, R381N, R382S, R382T, R382N, R382Q, R382D, R382E, R382A, K388S, K388T, K388N, K388Q, K388D, K388E, K388A, R389S, R389T, R389N, R389Q, R389D, R389E, R389A, K396S, K396T, K396N, K396Q, K396D, K396E, and K396A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0013] In some embodiments, the insertion is in the DNA binding domain (DBD) subdomain of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within an alpha helix, e.g., al5 or al6 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is within a loop, e.g., L20, L22, or L23 of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from any of amino acid positions 361-427, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation comprises an amino acid position selected from amino acid position 361, 381, 382, 388, 389, and 396, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from K361X, R381X, R382X, K388X, R389X, and K396X, wherein X is any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation is selected from K361S, K361T, K361N, K361Q, K361D, K361E, K361A, R381T, R381Q, R381N, R382S, R382T, R382N, R382Q, R382D, R382E, R382A, K388S, K388T, K388N, K388Q, K388D, K388E, K388A, R389S, R389T, R389N, R389Q, R389D, R389E, R389A, K396S, K396T, K396N, K396Q, K396D, K396E, and K396A, e g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0014] In another aspect, a reverse transcriptase comprises the following domains: (i) the reverse transcriptase (RT) domain (e.g., finger subdomain (e.g., the RTO motif) or the palm subdomain (e.g., the insertion in the finger domain (IFD) motif)); (ii) the thumb domain (e.g., the DNA binding domain (DBD)) of a reference sequence described herein, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In an embodiment, the reverse transcriptase further comprises one or more of the following amino acids: Q58, K58, S59, T59, N59, Q59, D59, E59, A59, S160, T160, N160, Q160, D160, E160, A160, S240, T240, N240, Q240, D240, E240, A240, S243, T243, N243, Q243, D243, E243, A243, S247, T247, N247, Q247, D247, E247, A247, S266, T266, N266, Q266, D266, E266, A266, S289, T289, N289, Q289, D289, E289, A289, S303, T3O3, N303, Q303, D3O3, E303, A303, S338, T338, N338, Q338, D338, E338, A338, S342, T342, N342, Q342, D342, E342, A342, S347, T347, N347, Q347, D347, E347, A347, T349, Q349, E349, A349, T351, Q351, N351, D351, E351, S351, A351, S358, T358, N358, Q358, D358, E358, A358, S361, T361, N361, Q361, D361, E361, A361, T381, Q381, N381, S382, T382, N382, Q382, D382, E382, A382, S388, T388, N388, Q388, D388, E388, A388, S389, T389, N389, Q389, D389, E389, A389, S396, T396, N396, Q396, D396, E396, and A396, relative to a reference sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In an embodiment, the reverse transcriptase further comprises one or more of the following amino acids: Q58, K58, S59, T59, N59, Q59, D59, E59, A59, S160, T160, N160, Q160, D160, E160, A160, S240, T240, N240, Q240, D240, E240, A240, S243, T243, N243, Q243, D243, E243, A243, S247, T247, N247, Q247, D247, E247, A247, S266, T266, N266, Q266, D266, E266, A266, E282, D282, S282, T282, N282, Q282, A282, S289, T289, N289, Q289, D289, E289, A289, Q293, R293, H293, D293, E293, N293, S293, T293, A293, S303, T303, N3O3, Q303, D303, E303, A303, E308, D308, N308, Q308, S308, T308, A308, S338, T338, N338, Q338, D338, E338, A338, S342, T342, N342, Q342, D342, E342, A342, S347, T347, N347, Q347, D347, E347, A347, T349, Q349, E349, A349, T351, Q351, N351, D351, E351, S351, A351, S358, T358, N358, Q358, D358, E358, A358, S361, T361, N361, Q361, D361, E361, A361, T381, Q381, N381, S382, T382, N382, Q382, D382, E382, A382, S388, T388, N388, Q388, D388, E388, A388, S389, T389, N389, Q389, D389, E389, A389, S396, T396, N396, Q396, D396, E396, and A396, relative to a reference sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2.

[0015] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in the RT domain (e g., finger subdomain (e.g., the RTO motif) or the palmsubdomain (e.g., the insertion in the finger domain (IFD) motif)): Q58, K58, S59, T59, N59, Q59, D59, E59, A59, S160, T160, N160, Q160, D160, E160, A160, S240, T240, N240, Q240, D240, E240, A240, S243, T243, N243, Q243, D243, E243, A243, S247, T247, N247, Q247, D247, E247, A247, S266, T266, N266, Q266, D266, E266, A266, S289, T289, N289, Q289, D289, E289, and A289, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in the RT domain (e.g., finger subdomain (e.g., the RTO motif) or the palm subdomain (e.g., the insertion in the finger domain (IFD) motif)): Q58, K58, S59, T59, N59, Q59, D59, E59, A59, S160, T160, N160, Q160, D160, E160, A160, S240, T240, N240, Q240, D240, E240, A240, S243, T243, N243, Q243, D243, E243, A243, S247, T247, N247, Q247, D247, E247, A247, S266, T266, N266, Q266, D266, E266, A266, E282, D282, S282, T282, N282, Q282, A282, S289, T289, N289, Q289, D289, E289, and A289, e g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0016] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in the finger subdomain (e.g., the RTO motif): Q58, K58, S59, T59, N59, Q59, D59, E59, and A59, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0017] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in the RTO motif (e.g., L4): Q58, K58, S59, T59, N59, Q59, D59, E59, and A59, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0018] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in L4: Q58, K58, S59, T59, N59, Q59, D59, E59, and A59, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0019] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in the palm subdomain (e.g., the insertion in the finger domain (IFD) motif), a7, alO, L15, or [36): S160, T160, N160, Q160, D160, E160, A160, S240, T240, N240, Q240, D240, E240, A240, S243, T243, N243, Q243, D243, E243, A243, S247, T247, N247, Q247, D247, E247, A247, S266, T266, N266, Q266, D266, E266, A266, S289, T289, N289, Q289, D289, E289, and A289, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0020] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in the insertion in the finger domain (IFD) motif (e.g., a7): S160, T160, N160, Q160, D160, E160, and A160, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0021] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in a7: S160, T160, N160, Q160, D160, E160, A160, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0022] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in alO: S240, T240, N240, Q240, D240, E240, A240, S243, T243, N243, Q243, D243, E243, A243, S247, T247, N247, Q247, D247, E247, and A247, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0023] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in L15: S266, T266, N266, Q266, D266, E266, and A266, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0024] In some embodiments, the reverse transcriptase comprises the following amino acid in L16: E282, D282, S282, T282, N282, Q282, A282, e.g, relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0025] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in (36: S289, T289, N289, Q289, D289, E289, and A289, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0026] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in the thumb domain (the DNA binding domain (DBD) subdomain, al l, al3, L20, al5, L22, al6, or L23): S3O3, T303, N303, Q3O3, D303, E303, A3O3, S338, T338, N338, Q338, D338, E338, A338, S342, T342, N342, Q342, D342, E342, A342, S347, T347, N347, Q347, D347, E347, A347, T349, Q349, E349, A349, T351, Q351, N351, D351, E351, S351, A351, S358, T358, N358, Q358, D358, E358, A358, S361, T361, N361, Q361, D361, E361, A361, T381, Q381, N381, S382, T382, N382, Q382, D382, E382, A382, S388, T388, N388, Q388, D388, E388, A388, S389, T389, N389, Q389, D389, E389, A389, S396, T396, N396, Q396, D396, E396, and A396,e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in the thumb domain (the DNA binding domain (DBD) subdomain, al l, al3, L18, L20, al5, L22, al6, or L23): Q293, R293, H293, D293, E293, N293, S293, T293, A293, S303, T303, N303, Q303, D3O3, E303, A303, E308, D308, N308, Q308, S308, T308, A308, S338, T338, N338, Q338, D338, E338, A338, S342, T342, N342, Q342, D342, E342, A342, S347, T347, N347, Q347, D347, E347, A347, T349, Q349, E349, A349, T351, Q351, N351, D351, E351, S351,A351 , S358, T358, N358, Q358, D358, E358, A358, S361 , T361, N361, Q361, D361, E361, A361, T381, Q381, N381, S382, T382, N382, Q382, D382, E382, A382, S388, T388, N388, Q388, D388, E388, A388, S389, T389, N389, Q389, D389, E389, A389, S396, T396, N396, Q396, D396, E396, and A396,e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0027] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in the DNA binding domain (DBD) subdomain (e.g., L20, al5, L22, al6, or L23): S361, T361, N361, Q361, D361, E361, A361, T381, Q381, N381, S382, T382, N382, Q382, D382, E382, A382, S388, T388, N388, Q388, D388, E388, A388, S389, T389, N389, Q389, D389, E389, A389, S396, T396, N396, Q396, D396, E396, and A396, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0028] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in al 1 : S303, T303, N3O3, Q303, D303, E303, and A303, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0029] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in al3: S338, T338, N338, Q338, D338, E338, A338, S342, T342, N342, Q342, D342, E342, A342, S347, T347, N347, Q347, D347, E347, A347, T349, Q349, E349, A349, T351, Q351, N351, D351, E351, S351, A351, S358, T358, N358, Q358, D358, E358, and A358, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0030] In some embodiments, the reverse transcriptase comprises the following amino acid in L18: E308, D308, N308, Q308, S308, T308, A308, e.g, relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0031] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in L20: S361, T361, N361, Q361, D361, E361, and A361, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0032] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in al5: T381, Q381, N381, S382, T382, N382, Q382, D382, E382, and A382, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0033] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in L22: S388, T388, N388, Q388, D388, E388, and A388, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0034] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in al6: S389, T389, N389, Q389, D389, E389, and A389, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0035] In some embodiments, the reverse transcriptase comprises one or more of the following amino acids in L23: S396, T396, N396, Q396, D396, E396, and A396, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0036] In another aspect, the reverse transcriptase comprises a mutation at each of amino acid positions: (i) 58 and 59; (ii) 243, 247, and 240; (iii) 282, 338, and 342; (iv) 303, 308, and 347; (v) 338 and 342; (vi) 303 and 308; (vii) 382, 388, and 389; or (viii) 361 and 388, wherein the amino acid positions correspond to an amino acid position in a reference sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2.

[0037] In some embodiments, the reverse transcriptase comprises mutations selected from: (i) R58X and K59X; (ii) R243X, R247X, and R240X; (iii) R282X, K338X, and K342X; (iv) K303X, R308X, and R347X; (v) K338X and K342X; (vi) K303X and R308X; (vii) R382X, K388X, and R389X; and (viii) K361X and K388X, wherein X denotes any amino acid, and wherein the amino acid positions correspond to an amino acid position in a reference sequence, e g., SEQ ID NO: 1 or SEQ ID NO: 2.

[0038] In some embodiments, the reverse transcriptase comprises R58Q and K59E mutations, relative to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises R58Q and K59S mutations, relative to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an R160Q mutation, relative to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises R243S, R247A, and R240S mutations, relative to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an R282E mutation, relative to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises a K293Q mutation, relative to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises R282E, K338E, and K342E mutations, relative to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises K303E, R308E, and R347Q mutations, relative to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises K338E and K342E mutations, relative to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises K303E and R308E mutations, relative to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprisesR382Q, K388E, and R389E mutations, relative to SEQ ID NO: 1 . In some embodiments, the reverse transcriptase comprises K361S and K388E mutations, relative to SEQ ID NO: 1.

[0039] In some embodiments, the reverse transcriptase comprises SEQ ID NO: 6, or a sequence with about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, 99.9%, or greater identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises SEQ ID NO: 7, or a sequence with about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, 99.9%, or greater identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises SEQ ID NO: 8, or a sequence with about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, 99.9%, or greater identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises SEQ ID NO: 9, or a sequence with about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, 99.9%, or greater identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises SEQ ID NO: 10, or a sequence with about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, 99.9%, or greater identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises SEQ ID NO: 11, or a sequence with about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, 99.9%, or greater identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises SEQ ID NO: 12, or a sequence with about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, 99.9%, or greater identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises SEQ ID NO: 13, or a sequence with about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, 99.9%, or greater identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises SEQ ID NO: 14, or a sequence with about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, 99.9%, or greater identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises SEQ ID NO: 15, or a sequence with about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, 99.9%, or greater identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises SEQ ID NO: 16, or a sequence with about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, 99.9%, or greater identity to SEQ ID NO: 16.

[0040] In another aspect, the reverse transcriptase comprises a mutation relative to a reference sequence in at least one of the following domains: (i) the reverse transcriptase (RT) domain (e.g., the finger subdomain or the palm subdomain); (ii) the thumb domain (e.g., the DNA binding domain (DBD) subdomain); wherein the reference sequence comprises a sequenceselected from SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5, or a fragment or variant thereof. In some embodiments, the reference sequence comprises SEQ ID NO: 3 or a fragment or variant thereof. In some embodiments, the reference sequence comprises SEQ ID NO: 4 or a fragment or variant thereof. In some embodiments, the reference sequence comprises SEQ ID NO: 5 or a fragment or variant thereof. In some embodiments, the mutation is a positively charged, negatively charged, or neutral mutation. In some embodiments, the mutation is at an arginine residue of a reference sequence described herein, e.g., SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the mutation is at a lysine residue of a reference sequence described herein, e.g., SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the mutation is within an alpha helix, a beta sheet, or a loop of a reference sequence described herein, e.g., SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the mutation is in the RT domain of a reference sequence described herein, e.g., SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the mutation is in the finger subdomain of a reference sequence described herein, e.g., SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the mutation is in the palm subdomain of a reference sequence described herein, e.g., SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the mutation is in the thumb domain of a reference sequence described herein, e.g., SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0041] In some embodiments, the mutation is in the DNA binding domain (DBD) subdomain of a reference sequence described herein, e.g., SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0042] In some embodiments, the reverse transcriptase comprises at least one mutation, e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more mutations, e.g., relative to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase has at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 99.9% sequence identity to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the mutation is at the interface between reverse transcriptase dimers of a reference sequence described herein, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the mutation is within a binding region, e.g., a DNA or RNA binding region, e.g., relative to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments,the mutation is within a DNA binding region, e.g., relative to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the mutation is within an RNA binding region, e.g., relative to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase is a template-switching reverse transcriptase.

[0043] In another aspect, the present disclosure features a method of performing reverse transcription comprising contacting a target RNA with the reverse transcriptase comprising a mutation relative to a reference sequence.

[0044] In another aspect, the present disclosure features a method for acquiring a value for the presence of a target ribonucleic acid (RNA) in a mixture, comprising contacting the mixture with: (i) the reverse transcriptase comprising a mutation relative to a reference sequence; (ii) an oligonucleotide primer; and (iii) a deoxynucleotide triphosphate (dNTP) solution; thereby acquiring a value for the presence of the target RNA.

[0045] In another aspect, the present disclosure features a method for synthesizing complementary DNA (cDNA) from a ribonucleic acid (RNA), e.g., a target RNA, in a mixture, comprising contacting the mixture with: (i) the reverse transcriptase comprising a mutation relative to a reference sequence; (ii) an oligonucleotide primer; and (iii) a deoxynucleotide triphosphate (dNTP) solution; thereby synthesizing cDNA.

[0046] In another aspect, the present disclosure features a method for acquiring a value for the presence of a target ribonucleic acid (RNA) in a mixture, comprising contacting the mixture with: (i) the reverse transcriptase comprising a mutation relative to a reference sequence; (ii) an oligonucleotide primer; (iii) a template switching oligonucleotide; and (iv) a deoxynucleotide triphosphate (dNTP) solution; thereby acquiring a value for the presence of the target RNA.

[0047] In another aspect, the present disclosure features a method for synthesizing complementary DNA (cDNA) from a ribonucleic acid (RNA), e.g., a target RNA, in a mixture, comprising contacting the mixture with: (i) the reverse transcriptase comprising a mutation relative to a reference sequence; (ii) an oligonucleotide primer; (iii) a template switching oligonucleotide; and (iv) a deoxynucleotide triphosphate (dNTP) solution; thereby synthesizing cDNA.

[0048] In another aspect, the present disclosure features a method of synthesizing complementary DNA (cDNA), e.g., from an RNA template, comprising contacting a target RNA with: (i) a reverse transcription primer; (ii) a template switching oligonucleotide; (iii) a deoxyribonucleotide triphosphate (dNTP) solution; and (iv) the reverse transcriptase comprising a mutation relative to a reference sequence; thereby synthesizing cDNA.

[0049] In yet another aspect, the present disclosure features a method of producing a complementary DNA (cDNA) library comprising cDNAs comprising sequences complementary to a plurality of target RNAs comprising contacting a plurality of target RNAs with: (i) a reverse transcription primer; (ii) a template switching oligonucleotide; (iii) a deoxyribonucleotide triphosphate (dNTP) solution; and (iv) the reverse transcriptase comprising a mutation relative to a reference sequence; thereby producing a cDNA library comprising sequences complementary to a plurality of target RNAs.BRIEF DESCRIPTION OF DRAWINGS

[0050] FIG. 1 is an image of the cryo-electron microscopy model (PDB ID: 7UIN) of MarathonRT in complex with DNA (blue) and intron RNA (orange). The domains of MarathonRT are indicated as labeled: RT0 domain (red), IFD (dark blue), palm domain (green), and thumb domain (cyan).

[0051] FIGS. 2A-2B are images of the crystal structure of MarathonRT shown in FIG. 1 with positively charged residues that interact with DNA or RNA labeled and highlighted in magenta. FIG. 2A shows exemplary positively charged residues in the RT0, IFD, and palm domains. FIG. 2B shows exemplary positively charged residues in the thumb domain.

[0052] FIG. 3 is a set of images of protein electrophoresis gels. The left image shows purified MarathonRT (SEQ ID NO: 1). The right image shows purified MarathonRT variants of SEQ ID NOs: 17, 6, 10, and 13.

[0053] FIG. 4 is an image of a protein electrophoresis gel showing pre-amplified cDNA libraries synthesized by wildtype MarathonRT (SEQ ID NO: 1) or MarathonRT variants of SEQ ID NOs: 11, 16, 17, 6, 7, 8, 9, 10, 12, 13, 14, and 15.DESCRIPTION

[0054] The present disclosure features a polymerase, e.g., a reverse transcriptase, e.g., MarathonRT or UltraMarathonRT, and fragments or variants thereof. As disclosed herein, variants of MarathonRT can have improved functional properties, e.g., stability, yield, or enzyme activity.Definitions

[0055] So that the disclosure may be more readily understood, certain technical and scientific terms used herein are specifically defined below. Unless specifically defined elsewhere in this document, all other technical and scientific terms used herein have the meaning commonly understood by one of ordinary skill in the art to which this disclosure belongs.

[0056] As used herein, including the appended claims, the singular forms of words such as "a," "an," and "the," include their corresponding plural references unless the context clearly dictates otherwise.

[0057] “About" or “approximately” means when used herein to modify a numerically defined parameter (e.g., yield of cDNA resulting from reverse transcription by a reverse transcriptase), means that the recited numerical value is within an acceptable functional range for the defined parameter as determined by one of ordinary skill in the art, which will depend in part on how the numerical value is measured or determined, e.g., the limitations of the measurement system, including the acceptable error range for that measurement system. For example, “about” can mean a range of 20% above and below the recited numerical value. As a non-limiting example, the concentration of an anionic polymer in a reaction mixture may be about 0.01 pg / pL to about 100 ng / pL. In some embodiments, the term “about” means that the modified parameter may vary by as much as 15%, 10% or 5% above and below the stated numerical value for that parameter. Alternatively, particularly with respect to certain properties of an anionic polymer in a reaction mixture, such as increasing the yield of cDNA produced from low abundance nucleic acids in a sample, the term “about” can mean within an order of magnitude above and below the recited value, e.g., within 5-fold, 4-fold, 3-fold, 2-fold or 1-fold.

[0058] “Acquire” or “acquiring”, as used herein, refers to obtaining possession of a value, e.g., a numerical value, or image, or a physical entity (e.g., a sample), by “directly acquiring” or “indirectly acquiring” the value or physical entity. “Directly acquiring” meansperforming a process (e.g., performing an analytical method or protocol) to obtain the value or physical entity. “Indirectly acquiring” refers to receiving the value or physical entity from another party or source (e.g., a third-party laboratory that directly acquired the physical entity or value). Directly acquiring a value or physical entity includes performing a process that includes a physical change in a physical substance or the use of a machine or device. Examples of directly acquiring a value include obtaining a sample from a human subject. Directly acquiring a value includes performing a process that uses a machine or device, e.g., using a fluorescence microscope to acquire fluorescence microscopy data.

[0059] A “nucleotide,” as that term is used herein, refers to an entity comprising a sugar, typically a pentameric sugar; a nucleobase; and a phosphate linking group. In an embodiment, a nucleotide comprises a naturally occurring, e.g., naturally occurring in a human cell, nucleotide, e g., an adenine, thymine, guanine, cytosine, or uracil nucleotide. “Nucleotide” may be abbreviated as “nt” herein. In an embodiment, a nucleotide comprises one, two, or three phosphate linking groups, e.g., the nucleotide is a nucleotide monophosphate, a nucleotide diphosphate, or a nucleotide triphosphate. The terms “nucleotide triphosphate” and “nucleoside triphosphate” are equivalent and interchangeable as used herein.

[0060] “Nucleic acid”, as used herein, refers to a polymer comprising a nucleotide linked through phosphodiester bonds. In an embodiment, a nucleic acid comprises at least two, and in some embodiments, at least 10, 100, 1,000, or 10,000 nucleotides. In some embodiments, a nucleic acid comprises ribonucleotides, e g., is a ribonucleic acid (RNA). In some embodiments, a nucleic acid comprises deoxyribonucleotides, e.g., is deoxyribonucleic acid (DNA). “Nucleic acid”, as used herein, is interchangeable with “polynucleotide” or “oligonucleotide”. The length of a nucleic acid is referred to herein as a number of bases, e.g., a nucleic acid comprising 1,000 nucleotides has a length of 1,000 bases or 1 kilobase (kb).

[0061] “Complementary DNA” or “cDNA”, as used herein, refers to the deoxyribonucleic acid (DNA) product synthesized through a reverse transcription reaction, e.g., DNA synthesized by reverse transcription using a ribonucleic acid (RNA) molecule as a substrate.

[0062] “Polypeptide”, as used herein, refers to a polymer comprising amino acid residues linked through peptide bonds and having at least two, and in some embodiments, at least 10, 50, 75, 100, 150 or 200 amino acid residues.

[0063] “Secondary structure”, as used herein, refers to the spatial conformation of a polypeptide backbone. Examples of secondary structure, e.g., within a protein, include alpha helices and beta sheets.

[0064] “Tertiary structure”, as used herein, refers to the three-dimensional shape of a protein. The tertiary structure of a protein comprises the secondary structure of the protein and unstructured regions, e.g., a loop. For example, the tertiary structure of a protein comprises the arrangement of the secondary structures and unstructured regions of a protein.

[0065] “Protein”, as used herein, refers to a polypeptide, wherein at least a portion of the polypeptide chain is capable of folding into secondary and / or tertiary structure. In some embodiments, a protein comprises a polypeptide chain of at least 50, 75, 100, 150, 200 or more amino acid residues. In some embodiments, a protein has a function, e.g., a structural or enzymatic function. A protein capable of enzymatic function, e.g., catalysis, is referred to as an enzyme. Examples of enzymes include polymerases, e.g., DNA polymerases, e.g., reverse transcriptases.

[0066] “Monomer”, as used herein, refers to a single unit of a protein. For example, a monomer is a single polypeptide chain of a protein amino acid sequence.

[0067] “Dimer”, as used herein, refers to two units of a protein in complex, e.g., bound, to one another. For example, a dimer comprises a first protein monomer bound to a second monomer.

[0068] “Domain”, as used herein, refers to a region of a polypeptide chain of a protein, e.g., an enzyme, e.g., a polymerase enzyme. In an embodiment, a domain folds independently from the rest of the polypeptide chain and is self-stabilizing. In another embodiment, a domain forms a distinct three-dimensional structure within a protein and may be capable of a function, e.g., a structural or enzymatic function. Examples of a structural function include stabilizing an interaction, e.g., an interaction a different protein, another domain within the same protein, a macromolecule, or a small molecule, promoting protein folding, e.g., folding of a different protein or another domain within the same protein, or promoting stability of the protein, e.g., increasing the half-life of the protein. An enzymatic function, for example, may comprise polymerizing nucleotides into polynucleotide strands. Examples of domains include a DNA or RNA binding domain, e.g., a domain capable of binding DNA or RNA, a polymerase domain, e g., a domain capable of polymerizing, for example, DNA or RNA polynucleotides, or astructural domain, e.g., a domain capable of stabilizing or enhancing the activity of another domain within the protein. A domain may be connected by a loop, e.g., an unstructured or flexible region, e.g., a region without defined secondary structure.

[0069] “Subdomain”, as used herein, refers to a structural unit within a domain of a protein comprising secondary structure, e.g., an alpha helix or beta sheet, distinct from other secondary structure within the domain. A subdomain may be defined by secondary structures, e.g., alpha helices or beta sheets, in close proximity within a folded protein structure. For example, adjacent alpha helices or adj cent beta sheets may form a subdomain. A subdomain may be capable of a function, e.g., a structural or enzymatic function.

[0070] “Motif’, as used herein, refers to a three-dimensional arrangement of secondary structures within a protein, e.g., arrangement of alpha helices or beta sheets. Motifs may be conserved amongst related proteins or proteins of diverse evolutionary backgrounds. Examples of motifs include two antiparallel alpha helices connected by a loop, or four alpha helices connected by loops that form two sets of antiparallel helices.

[0071] The term “template” as used herein, with respect to a polynucleotide, refers to a single-stranded polynucleotide substrate for a nucleic acid polymerase, e.g., a reverse transcriptase. For example, a nucleic acid polymerase, e.g., a reverse transcriptase, can synthesize a polynucleotide strand that is complementary to the template strand. In some embodiments, a single-stranded RNA polynucleotide can be a template for a reverse transcriptase. A “template" polynucleotide, as used herein, may also be referred to as a “target” polynucleotide. In some embodiments, a target polynucleotide is RNA. In some embodiments, a target polynucleotide is DNA. The term “product” as used herein, with respect to a polynucleotide, refers to the polynucleotide strand synthesized by a nucleotide polymerase. In some embodiments, the nucleotide polymerase is a reverse transcriptase. In some embodiments, the product polynucleotide is a deoxyribonucleic acid (DNA) polynucleotide synthesized by a reverse transcriptase using a ribonucleic acid (RNA) polynucleotide as a template.

[0072] The term “target” as used herein, with respect to a polynucleotide, refers to a polynucleotide intended for detection by a reverse transcriptase, e.g., a polynucleotide for which a value is acquired using a method of reverse transcription. For example, the oligonucleotide primers in a reverse transcription reaction mixture are complementary to the target polynucleotide, thereby allowing the target polynucleotide to be reverse transcribed. In someembodiments, the target polynucleotide comprises a deoxyribonucleic acid (DNA). In some embodiments, the target polynucleotide comprises a ribonucleic acid (RNA).

[0073] The term “reverse transcription” as used herein, with respect to a subject molecule, e.g., a RNA polynucleotide, refers to synthesis of a deoxyribonucleic acid (DNA), e.g., cDNA, polynucleotide using a ribonucleic acid (RNA) polynucleotide as a template.

[0074] The term “reverse transcriptase activity” as used herein, refers to the capacity of an enzyme, e.g., a polymerase, to perform reverse transcription, e.g., perform a reverse transcription reaction. For example, an enzyme having reverse transcription activity is capable of synthesizing a DNA polynucleotide from an RNA polynucleotide template. The terms “reverse transcription activity” and “reverse transcriptase activity” are used interchangeably herein.

[0075] The term “reverse transcriptase” as used herein refers a nucleic acid polymerase capable of synthesizing a deoxyribonucleic acid (DNA) polynucleotide from a template ribonucleic acid (RNA) polynucleotide. For example, a reverse transcriptase may synthesize a single-stranded complementary DNA (cDNA) polynucleotide product from a messenger RNA (mRNA) expressed in a cell or subject. In some embodiments, a reverse transcriptase may be a template-switching reverse transcriptase. In some embodiments, the reverse transcriptase comprises a MarathonRT reverse transcriptase or an UltraMarathonRT reverse transcriptase, as well as variants, fragments, and mutants thereof.

[0076] The term “non-templated nucleotide addition” as used herein refers to the addition of nucleotides to the 3’ end of a product polynucleotide synthesized by an enzyme upon reaching the 5’ terminus of a template polynucleotide, e.g., addition of nucleotides to the product polynucleotide that are not comprised in the template polynucleotide. For example, non- templated nucleotide addition can result in a product polynucleotide that comprises a 3’ end which extends beyond the 5’ end of the template polynucleotide and is non-complementary to the template polynucleotide. Typically, non-templated nucleotide addition results in a 1-3 nucleotide overhang, e.g., 1, 2, or 3 nucleotide overhang, at the 3’ end of the product polynucleotide relative to the template polynucleotide.

[0077] The term “template switching” as used herein refers to the process of a polymerase enzyme switching from a first template polynucleotide to a second template polynucleotide while synthesizing a continuous product polynucleotide. Typically, template switching comprises: (i) non-templated nucleotide addition of nucleotides to the 3’ end of thepolynucleotide synthesized by the reverse transcriptase upon reaching the 5’ terminus of the template polynucleotide; (ii) base pairing between a template switching oligonucleotide (TSO) and the nucleotide overhang resulting from non-templated addition; and (iii) continued synthesis of the product polynucleotide by the reverse transcriptase using the TSO as the template polynucleotide.

[0078] The term “template switching activity” as used herein, refers to the capacity of an enzyme, e.g., a polymerase, to perform template switching, e.g., perform a template switching reaction. For example, an enzyme having template switching activity is capable of non-templated nucleotide addition, e.g., continuing polynucleotide synthesis without a template sequence upon reaching the 3’ terminus of the template polynucleotide, and switching template polynucleotides, e.g., continuing polynucleotide synthesis upon base pairing of a template switching oligonucleotide (TSO) to the nucleotides added by non-templated nucleotide addition.

[0079] The term “concatemerization” as used herein refers to the linkage of a plurality of the same polynucleotide sequence in series, e.g., the linkage of a plurality of template switching oligonucleotide (TSO) sequences. In some embodiments, concatemerization of a plurality of a TSO can be a result of repeated cycles of non-templated nucleotide addition by a reverse transcriptase followed by template switching by the reverse transcriptase.

[0080] “Carrier RNA” as used herein refers to a supplemental ribonucleic acid (RNA) molecule that improves the yield of enzymatic reactions on nucleic acids, e.g. cDNA produced during reverse transcription, e.g., an RNA molecule that is present in the reaction mixture but is not a target RNA. Typically, a carrier RNA stabilizes template RNA. Alternatively, carrier RNA may improve reverse transcription activity.

[0081] “Polymerase” or “polymerase enzyme”, as used herein, refers to an enzyme capable of forming phosphodiester linkages between nucleotides, e.g., ribonucleotides or deoxyribonucleotides, in a manner that is directed by a template polynucleotide, e.g., a template ribonucleic acid (RNA) or template deoxyribonucleic acid (DNA), thereby generating a polynucleotide strand that is complementary to the template polynucleotide. Polymerases may use RNA templates, e.g., be RNA-dependent, or DNA templates, e.g., be DNA-dependent. Additionally, polymerases may utilize ribonucleotides to synthesize RNA polynucleotides or utilize deoxyribonucleotides to synthesize DNA polynucleotides. In some embodiments, a polymerase is a reverse transcriptase.Polymerase Enzymes

[0082] The present disclosure features polymerases, e.g., reverse transcriptases, or fragments or variants thereof with improved enzyme activity, yield, or stability. Polymerases are enzymes that catalyze phosphodiester bond formation between nucleotides, e.g., ribonucleotides or deoxyribonucleotides, to generate a polynucleotide product, e.g., a ribonucleic acid (RNA) or a deoxyribonucleic acid (DNA), in a sequence-directed manner. For example, polymerases synthesize polynucleotide products that are complementary in sequence to a template nucleic acid, e.g., a template RNA molecule or template DNA molecule. Polymerases are categorized by the type of nucleic acid synthesized and the type of nucleic acid used as a template, e g., RNA or DNA. For example, polymerases can be RNA polymerases, e.g., synthesize RNA products, or DNA polymerases, e.g., synthesize DNA products. As a further example, polymerases can be RNA-dependent, e.g., use RNA as a template, or DNA-dependent, e.g., use DNA as a template. Thus, polymerases are generally categorized as being RNA-dependent RNA polymerases, RNA- dependent DNA polymerases, DNA-dependent RNA polymerases, or DNA-dependent DNA polymerases. In some embodiments, the present disclosure relates to RNA-dependent DNA polymerases, e g., reverse transcriptases.

[0083] Reverse transcriptases are polymerases that synthesize single-stranded complementary DNA (cDNA) from a single-stranded RNA template. Reverse transcriptases are useful for methods of analyzing gene expression by measuring abundance of messenger RNA (mRNA) such as reverse transcription coupled to quantitative polymerase chain reaction (qRT- PCR) or RNA sequencing (RNA-seq). However, the accuracy of these methods can often be limited by the ability of a reverse transcriptase to reverse transcribe long template RNAs or RNAs with complex secondary structures from end-to-end, e.g., the ability of the reverse transcriptase to synthesize full-length cDNAs, e.g., the processivity of the reverse transcriptase. Additionally, methods for measuring gene expression can further be limited by the ability of a reverse transcriptase to reverse transcribe low-abundance RNAs. For example, certain reverse transcriptases are unable to amplify meaningful amounts of low-abundance RNAs in complex mixtures, which can impact their utility in a research or commercial setting, e g., in methods of measuring gene expression from samples with low amounts of input RNA, such as single-cell RNA sequencing or in situ RNA sequencing.

[0084] A polymerase, e.g., reverse transcriptase, or fragment or variant thereof described herein may be capable of improved enzyme activity, e.g., relative to polymerases known in the art. For example, a polymerase, e.g., reverse transcriptase, described herein may be capable of improved reverse transcriptase activity, terminal transferase activity, or template switching activity. In some embodiments, the polymerase capable of an improved enzyme activity is a reverse transcriptase. In some embodiments, the reverse transcriptase is capable of improved reverse transcriptase activity. In some embodiments, the reverse transcriptase is capable of improved terminal transferase activity. In some embodiments, the reverse transcriptase is capable of improved template switching activity. In some embodiments, the reverse transcriptase is capable of an improved ability to synthesize cDNAs, e.g., ability to synthesize full-length cDNAs or cDNAs from long or complex RNA templates. In some embodiments, the reverse transcriptase is capable of improved processivity during reverse transcription. In some embodiments, the reverse transcriptase is capable of synthesizing cDNA from RNA with low abundance in a sample. In some embodiments, the reverse transcriptase is capable of improved stability. In some embodiments, the reverse transcriptase is capable of improved purification yield.

[0085] In some embodiments, the polymerase or fragment or derivative thereof described herein is derived from a reverse transcriptase. In some embodiments, the reverse transcriptase is derived from a virus, an intron, a telomerase, or a retrotransposon. In some embodiments, the reverse transcriptase is derived from a mobile genetic element, e.g., a self-splicing intron, e.g., a non-long terminal repeat (non-LTR) retrotransposon, e.g., a group II intron. In some embodiments, the reverse transcriptase is derived from an engineered polymerase with reverse transcriptase activity. In some embodiments, the reverse transcriptase comprises a fragment or variant of a group II intron reverse transcriptase, or an engineered polymerase with reverse transcriptase activity.

[0086] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a non-LTR retrotransposon reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a group II intron reverse transcriptase amino acid sequence, e.g., a maturase reverse transcriptase amino acid sequence. In some embodiments, the group II intron reverse transcriptase comprises a maturase amino acidsequence. In some embodiments, the reverse transcriptase comprises a thermostable group II intron reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises an Eubacterium rectale group II intron reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a Roseburia intestinalis group II intron reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a Thermosynechococcus elongatus group II intron reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a Geobacillus stearothermophilus group II intron reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a MarathonRT group II intron reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises an UltraMarathonRT group II intron reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises an Induro RT group II intron reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a TGIRT group II intron reverse transcriptase amino acid sequence.

[0087] In some embodiments, the polymerase, e.g., reverse transcriptase, comprises a fragment or variant of a reverse transcriptase amino acid sequence. In some embodiments, a reverse transcriptase fragment comprises a partial reverse transcriptase sequence, e.g., a sequence comprising at least one fewer amino acids than a reference reverse transcriptase sequence. In some embodiments, a reverse transcriptase variant comprises a reverse transcriptase sequence comprising a mutation, e.g., a substitution, deletion, or addition of a nucleotide or amino acid. In some embodiments, the reverse transcriptase comprises a fragment or variant of a group II intron reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a fragment or variant of a MarathonRT reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a fragment or variant of an UltraMarathonRT reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a fragment or variant of an Eubacterium rectale group II intron reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a fragment or variant of a Roseburia intestinalis group II intron reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a fragment or variant of a Thermosynechococcus elongatus group II intron reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a fragment or variant of a Geobacillusstearothermophilus group II intron reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a fragment or variant of an Induro RT group II intron reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a fragment or variant of a TGIRT group II intron reverse transcriptase amino acid sequence.Reference Sequences

[0088] In some embodiments, a polymerase, e.g., reverse transcriptase, or fragment or variant thereof described herein comprises a sequence, e.g., an amino acid sequence, e.g., relative to a reference sequence. In some embodiments, the reference sequence comprises the amino acid sequence of a reverse transcriptase, e.g., a group II intron reverse transcriptase, or a fragment or variant thereof. In some embodiments, the reference sequence comprises the amino acid sequence of a group II intron reverse transcriptase encoded by a bacterium, e.g., Eubacterium rectale, Roseburia intestinalis, Thermosynechococcus elongatus, or Geobacillus stearothermophilus, or a fragment or variant thereof. In some embodiments, the reference sequence comprises the amino acid sequence of a group II intron reverse transcriptase encoded by a thermophilic bacterium, e.g., Eubacterium rectale, Roseburia intestinalis, Thermosynechococcus elongatus, or Geobacillus stearothermophilus, or a fragment or variant thereof In some embodiments, the reference sequence comprises the amino acid sequence of a group II intron reverse transcriptase, e g., a MarathonRT, UltraMarathonRT, TGIRT, or Induro RT reverse transcriptase, or a fragment or variant thereof. In some embodiments, the reference sequence comprises the amino acid sequence of a MarathonRT reverse transcriptase, or a fragment or variant thereof. In some embodiments, the reference sequence comprises the amino acid sequence of an UltraMarathonRT reverse transcriptase, or a fragment or variant thereof. In some embodiments, the reference sequence comprises the amino acid sequence of a TGIRT reverse transcriptase, or a fragment or variant thereof. In some embodiments, the reference sequence comprises the amino acid sequence of an Induro RT reverse transcriptase, or a fragment or variant thereof. In some embodiments, the reference sequence comprises an amino acid sequence listed in Table 1, e.g, SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, or a fragment or variant thereof. In some embodiments, the reference sequence comprises SEQ ID NO: 1, or a fragment or variant thereof. In some embodiments, thereference sequence comprises SEQ TD NO: 2, or a fragment or variant thereof. In some embodiments, the reference sequence comprises SEQ ID NO: 3, or a fragment or variant thereof. In some embodiments, the reference sequence comprises SEQ ID NO: 4, or a fragment or variant thereof. In some embodiments, the reference sequence comprises SEQ ID NO: 5, or a fragment or variant thereof.Table 1. Exemplary reverse transcriptase sequences.

[0089] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises an amino acid sequence that has sequence identity to a reference sequence, e.g., has partial sequence identity to a reference sequence. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to a reference sequence, e g., a reverse transcriptase amino acid sequence, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequencethat has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%,99.5%, or 99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 18. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 19. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 20. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 21. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 22. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 23. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 24. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 25. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 26. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 27. In some embodiments, the reversetranscriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 28. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 29. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 30. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 31. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 32. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 33. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 34. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 35. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 36. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 37. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 38. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 39. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%,75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 40. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 41. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 42. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 43. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 44. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 45. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 46. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 47. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 48. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 49. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 50. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 51. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQID NO: 52. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 53. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 54. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 55. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 56. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 57. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 58. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 59. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 60. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 61. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 62. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 63. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 64. In some embodiments, the reverse transcriptase comprises an amino acid sequencethat has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to SEQ ID NO: 65. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to any one of SEQ ID NOs: 1-5 and 18-65. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40%, 50%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 99.9% sequence identity to any one of SEQ ID NOs: 1-65.

[0090] In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQID NO: 1 . In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequencethat has at least 60% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 4. In some embodiments, the reversetranscriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ IDNO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequencethat has at least 40% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 8. In some embodiments, the reversetranscriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises amino acid sequence thathas at least 99.5% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 12. In some embodiments, the reversetranscriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence thathas at least 98% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 16. In some embodiments, the reversetranscriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 40% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 50% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 60% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 65% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 70% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 75% sequence identity to SEQID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 80% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 85% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 90% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 95% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 96% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 97% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 98% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises amino acid sequence that has at least 99.5% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has at least 99.9% sequence identity to SEQ ID NO: 17.

[0091] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises an amino acid sequence that has between 40-99.9%, 50-99.9%, 60- 99.9%, 65-99.9%, 70-99.9%, 75-99.9%, 80-99.9%, 85-99.9%, 90-99.9%, 95-99.9%, 96-99.9%, 97-99.9%, 98-99.9%, 99-99.9%, or 99.5-99.9% sequence identity to a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises an amino acid sequence that has between 40-99.9%, 50-99.9%, 60-99.9%, 65-99.9%, 70-99.9%, 75-99.9%, 80-99.9%, 85-99.9%, 90-99.9%, 95-99.9%, 96-99.9%, 97-99.9%, 98- 99.9%, 99-99.9%, or 99.5-99.9% sequence identity to a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9%, 50- 99.9%, 60-99.9%, 65-99.9%, 70-99.9%, 75-99.9%, 80-99.9%, 85-99.9%, 90-99.9%, 95-99.9%, 96-99.9%, 97-99.9%, 98-99.9%, 99-99.9%, or 99.5-99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9%, 50-99.9%, 60-99.9%, 65-99.9%, 70-99.9%, 75-99.9%, 80-99.9%, 85-99.9%,90-99.9%, 95-99.9%, 96-99.9%, 97-99.9%, 98-99.9%, 99-99.9%, or 99.5-99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9%, 50-99.9%, 60-99.9%, 65-99.9%, 70-99.9%, 75-99.9%, 80-99.9%, 85-99.9%, 90-99.9%, 95-99.9%, 96-99.9%, 97-99.9%, 98-99.9%, 99-99.9%, or 99.5- 99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9%, 50-99.9%, 60-99.9%, 65-99.9%, 70-99.9%, 75-99.9%, 80-99.9%, 85-99.9%, 90-99.9%, 95-99.9%, 96-99.9%, 97-99.9%, 98- 99.9%, 99-99.9%, or 99.5-99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9%, 50-99.9%, 60-99.9%, 65-99.9%, 70-99.9%, 75-99.9%, 80-99.9%, 85-99.9%, 90-99.9%, 95-99.9%, 96- 99.9%, 97-99.9%, 98-99.9%, 99-99.9%, or 99.5-99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 50-99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70-99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75-99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 80-99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 85- 99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97-99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98-99.9% sequenceidentity to SEQ ID NO: 1 . In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99-99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5- 99.9% sequence identity to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 50-99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70-99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75-99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between SO- 99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 85-99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97-99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98-99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99- 99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5-99.9% sequence identity to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 50-99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acidsequence that has between 60-99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70-99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75- 99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 80-99.9% sequence identity to SEQ ID NO:3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 85-99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97-99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98- 99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99-99.9% sequence identity to SEQ ID NO:3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5-99.9% sequence identity to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 50-99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70- 99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75-99.9% sequence identity to SEQ ID NO:4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 80-99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reversetranscriptase comprises an amino acid sequence that has between 85-99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97- 99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98-99.9% sequence identity to SEQ ID NO:4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99-99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5-99.9% sequence identity to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 50-99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65- 99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70-99.9% sequence identity to SEQ ID NO:5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75-99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 80-99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 85-99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96- 99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97-99.9% sequence identity to SEQ ID NO:5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98-99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99-99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5-99.9% sequence identity to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40- 99.9% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 50-99.9% sequence identity to SEQ ID NO:6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70-99.9% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75-99.9% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 80-99.9% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 85- 99.9% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO:6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97-99.9% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98-99.9% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99-99.9% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5- 99.9% sequence identity to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9% sequence identity to SEQ ID NO:7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that hasbetween 50-99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70-99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75-99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between SO- 99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 85-99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97-99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98-99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99- 99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5-99.9% sequence identity to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 50-99.9% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70-99.9% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75- 99.9% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptasecomprises an amino acid sequence that has between 80-99.9% sequence identity to SEQ ID NO:8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 85-99.9% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97-99.9% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98- 99.9% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99-99.9% sequence identity to SEQ ID NO:8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5-99.9% sequence identity to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 50-99.9% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70- 99.9% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75-99.9% sequence identity to SEQ ID NO:9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 80-99.9% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 85-99.9% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 9. In someembodiments, the reverse transcriptase comprises an amino acid sequence that has between 97- 99.9% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98-99.9% sequence identity to SEQ ID NO:9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99-99.9% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5-99.9% sequence identity to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between SO- 99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO:10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70-99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75-99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between SO- 99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 85-99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97- 99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98-99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99-99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5-99.9% sequence identity to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises an amino acidsequence that has between 40-99.9% sequence identity to SEQ ID NO: 11 . In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between SO- 99.9% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO:11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70-99.9% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75-99.9% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between SO- 99.9% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 85-99.9% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97- 99.9% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98-99.9% sequence identity to SEQ ID NO:11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99-99.9% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5-99.9% sequence identity to SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 50- 99.9% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO:12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70-99.9% sequence identity toSEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75-99.9% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between SO- 99.9% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 85-99.9% sequence identity to SEQ ID NO:12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97- 99.9% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98-99.9% sequence identity to SEQ ID NO:12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99-99.9% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5-99.9% sequence identity to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 50- 99.9% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO:13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70-99.9% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75-99.9% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between SO- 99.9% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 85-99.9% sequence identity to SEQ ID NO:13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 13. In some embodiments, the reversetranscriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97- 99.9% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98-99.9% sequence identity to SEQ ID NO:13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99-99.9% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5-99.9% sequence identity to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 50- 99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO:14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70-99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75-99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between SO- 99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 85-99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97- 99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98-99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that hasbetween 99-99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5-99.9% sequence identity to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between SO- 99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70-99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75-99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between SO- 99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 85-99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97- 99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98-99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99-99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5-99.9% sequence identity to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between SO- 99.9% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO:16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70-99.9% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75-99.9% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between SO- 99.9% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 85-99.9% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97- 99.9% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98-99.9% sequence identity to SEQ ID NO:16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99-99.9% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5-99.9% sequence identity to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 40-99.9% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between SO- 99.9% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 60-99.9% sequence identity to SEQ ID NO:17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 65-99.9% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 70-99.9% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 75-99.9% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between SO- 99.9% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptasecomprises an amino acid sequence that has between 85-99.9% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 90-99.9% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 95-99.9% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 96-99.9% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 97- 99.9% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 98-99.9% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99-99.9% sequence identity to SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between 99.5-99.9% sequence identity to SEQ ID NO: 17.

[0092] In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between about 40-99.9% sequence identity, e.g., between about 50-99.9%, 60- 99.9%, 65-99.9%, 70-99.9%, 75-99.9%, 80-99.9%, 85-99.9%, 90-99.9%, 95-99.9%, 96-99.9%, 97-99.9%, 98-99.9%, 99-99.9%, or 99.5-99.9% sequence identity, to any one of SEQ ID NOs: 1- 65. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between about 40-99.9% sequence identity, e.g., between about 50-99.9%, 60-99.9%, 65-99.9%, 70-99.9%, 75-99.9%, 80-99.9%, 85-99.9%, 90-99.9%, 95-99.9%, 96-99.9%, 97-99.9%, 98- 99.9%, 99-99.9%, or 99.5-99.9% sequence identity, to any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the reverse transcriptase comprises an amino acid sequence that has between about 40-99.9% sequence identity, e.g., between about 50-99.9%, 60-99.9%, 65-99.9%, 70- 99.9%, 75-99.9%, 80-99.9%, 85-99.9%, 90-99.9%, 95-99.9%, 96-99.9%, 97-99.9%, 98-99.9%, 99-99.9%, or 99.5-99.9% sequence identity, to any one of SEQ ID NOs: 1-5 and 18-65.

[0093] In some embodiments, the polymerase, e.g., reverse transcriptase, comprises a fragment or variant of a reference sequence, e g., a reverse transcriptase amino acid sequence, e.g., any one of SEQ ID NO: 1-65. In some embodiments, the reverse transcriptase comprises a fragment or variant of a reverse transcriptase amino acid sequence. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 2. In someembodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 18. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 18. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 20. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 21. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 22. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 23. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 24. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 25. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 26. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 27. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 28. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 29. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 30. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 31. Insome embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 32. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 33. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 34. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 35. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 36. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 37. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 38. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 39. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 40. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 41. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 42. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 43. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 44. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 45. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 46. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 47. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 48. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 49. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 50. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 51. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 52. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 53. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 54. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 55. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 56. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 57. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 58. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 59. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 60.'llIn some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 61. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 62. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 63. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 64. In some embodiments, the reverse transcriptase comprises a fragment or variant of SEQ ID NO: 65. In some embodiments, the reverse transcriptase comprises a fragment or variant of any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises a fragment or variant of any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the reverse transcriptase comprises a fragment or variant of any one of SEQ ID NOs: 1-5 and 18-65.

[0094] In some embodiments, the reverse transcriptase comprises a fragment of a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., any one of SEQ ID NO: 1-65, wherein the fragment comprises at least one fewer amino acids than the reference sequence, e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 fewer amino acids than a reference sequence, e.g., at the N terminus or the C terminus. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 16. In someembodiments, the reverse transcriptase comprises a fragment of SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises a fragment of any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises a fragment of any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the reverse transcriptase comprises a fragment of any one of SEQ ID NOs: 1-5 and 18-65.

[0095] In some embodiments, the reverse transcriptase comprises 1 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 2 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 3 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 4 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 5 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 6 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 7 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 8 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 9 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 10 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 11 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 12 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 13 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 14 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 15 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 16 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 17 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 18 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 19 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 20 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises more than 20 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 1 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 2 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 3 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 4 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 5 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 6 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 7 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 8 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 9 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ IDNOs: 1-65. In some embodiments, the reverse transcriptase comprises 10 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 11 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 12 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 13 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 14 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 15 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 16 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 17 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 18 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 19 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 20 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises more than 20 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1 and about 50 fewer amino acids, e.g., between about 1-50, 1-40, 1-30, 1-20, 1-15, 1-10, or 1-5 fewer amino acids, than any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1 and about 50 fewer amino acids, e g., between about 1-50, 1-40, 1-30, 1-20, 1- 15, 1-10, or 1-5 fewer amino acids, than any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the reverse transcriptase comprises between about 1 and about 50 fewer amino acids, e g., between about 1-50, 1-40, 1-30, 1-20, 1-15, 1-10, or 1-5 fewer amino acids, than any one of SEQ ID NOs: 1-5 and 18-65.

[0096] In some embodiments, the reverse transcriptase comprises 1 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 2fewer amino acids at the N terminus than a reference sequence, e g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 3 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 4 fewer amino acids at the N terminus than a reference sequence, e g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 5 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 6 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 7 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 8 fewer amino acids at the N terminus than a reference sequence, e g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 9 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 10 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 11 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 12 fewer amino acids at the N terminus than a reference sequence, e g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 13 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 14 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 15 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In someembodiments, the reverse transcriptase comprises 16 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 17 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 18 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 19 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 20 fewer amino acids at the N terminus than a reference sequence, e g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises more than 20 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 1 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 2 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 3 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 4 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 5 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 6 fewer amino acids at the N terminus than a sequence provided in Table 1, e g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 7 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 8 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 9 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 10 fewer amino acids at the N terminus than a sequence providedin Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 11 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 12 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 13 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 14 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 15 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 16 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 17 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 18 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 19 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 20 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises more than 20 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1 and about 50 fewer amino acids at the N terminus, e.g., between about 1-50, 1- 40, 1-30, 1-20, 1-15, 1-10, or 1-5 fewer amino acids at the N terminus, than any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1 and about 50 fewer amino acids at the N terminus, e.g., between about 1-50, 1-40, 1-30, 1-20, 1-15, 1-10, or 1-5 fewer amino acids at the N terminus, than any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the reverse transcriptase comprises between about 1 and about 50 fewer amino acids at the N terminus, e.g., between about 1-50, 1-40, 1-30, 1-20, 1-15, 1-10, or 1-5 fewer amino acids at the N terminus, than any one of SEQ ID NOs: 1-5 and 18-65.

[0097] In some embodiments, the reverse transcriptase comprises 1 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3,SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 2 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 3 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 4 fewer amino acids at the C terminus than a reference sequence, e g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 5 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 6 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 7 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 8 fewer amino acids at the C terminus than a reference sequence, e g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 9 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 10 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 11 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 12 fewer amino acids at the C terminus than a reference sequence, e g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 13 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 14 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 1 fewer amino acids at the C terminus than a reference sequence, e.g.,SEQ ID NO: 1 , SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 16 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 17 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 18 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 19 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 20 fewer amino acids at the C terminus than a reference sequence, e g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises more than 20 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises 1 fewer amino acids at the C terminus than a sequence provided in Table 1, e g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 2 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 3 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 4 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 5 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 6 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 7 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 8 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 9 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, thereverse transcriptase comprises 10 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 11 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 12 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 13 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 14 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 15 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 16 fewer amino acids at the C terminus than a sequence provided in Table 1, e g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 17 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 18 fewer amino acids at the C terminus than a sequence provided in Table 1, e g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 19 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises 20 fewer amino acids at the C terminus than a sequence provided in Table 1, e g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises more than 20 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1 and about 50 fewer amino acids at the C terminus, e.g., between about 1-50, 1- 40, 1-30, 1-20, 1-15, 1-10, or 1-5 fewer amino acids at the C terminus, than any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1 and about 50 fewer amino acids at the C terminus, e.g., between about 1-50, 1-40, 1-30, 1-20, 1-15, 1-10, or 1-5 fewer amino acids at the C terminus, than any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the reverse transcriptase comprises between about 1 and about 50 fewer amino acids at the C terminus, e.g., between about 1-50, 1-40, 1-30, 1-20, 1-15, 1-10, or 1-5 fewer amino acids at the C terminus, than any one of SEQ ID NOs: 1-5 and 18-65.

[0098] In some embodiments, the reverse transcriptase comprises a fragment of a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., any one of SEQ ID NOs: 1-65, wherein the fragment comprises between 1 and 20 fewer amino acids than a reference sequence, e.g., between 1-20, 5-20, 10-20, or 15-20 fewer amino acids than a reference sequence, e.g., at the N terminus or the C terminus. In some embodiments, the reverse transcriptase comprises a fragment of a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g, SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5, wherein the fragment comprises between 1 and 20 fewer amino acids than a reference sequence, e.g., between 1-20, 5-20, 10-20, or 15-20 fewer amino acids than a reference sequence, e.g., at the N terminus or the C terminus. In some embodiments, the reverse transcriptase comprises between 1-20 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between 5-20 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between 10-20 fewer amino acids than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between 15-20 fewer amino acids than a reference sequence, e g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between 1-20 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between 5-20 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between 10-20 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between 15- 20 fewer amino acids at the N terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between 1-20 fewer amino acids at the C terminus than a reference sequence, e g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between 5-20 fewer amino acids atthe C terminus than a reference sequence, e.g., SEQ ID NO: 1 , SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between 10-20 fewer amino acids at the C terminus than a reference sequence, e.g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between 15-20 fewer amino acids at the C terminus than a reference sequence, e g., SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5.

[0099] In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids, e.g., about 1-20, 1-15, 1-10, or 1-5 fewer amino acids, than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids than SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids than SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises between about 1- 15 fewer amino acids than SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 3. In some embodiments, thereverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises between about 1- 15 fewer amino acids than SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between about 1- 15 fewer amino acids than SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises between about 1- 15 fewer amino acids than SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises between about 1- 15 fewer amino acids than SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises between about 1- 15 fewer amino acids than SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises between about 1- 15 fewer amino acids than SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 9. Insome embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids than SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids than SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids than SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids than SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids than SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids than SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises between about1-20 fewer amino acids than SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids than SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids than SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids than SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids than SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids than SEQ ID NO: 17.

[0100] In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus at the N terminus, e.g., about 1-15, 1-10, or 1-5 fewer amino acids at the N terminus at the N terminus, than a sequence provided in Table 1, e g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1- 20 fewer amino acids at the N terminus at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprisesbetween about 1 -10 fewer amino acids at the N terminus than SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 7. In someembodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the Nterminus than SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the N terminus than SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the N terminus than SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the N terminus than SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the N terminus than SEQ ID NO: 17.

[0101] In some embodiments, the reverse transcriptase comprises between about 1 -20 fewer amino acids at the C terminus at the C terminus, e.g., about 1-15, 1-10, or 1-5 fewer amino acids at the C terminus at the C terminus, than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1- 20 fewer amino acids at the C terminus at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than a sequence provided in Table 1, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 4. In someembodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the Cterminus than SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 11. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprisesbetween about 1 -10 fewer amino acids at the C terminus than SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises between about 1-20 fewer amino acids at the C terminus than SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises between about 1-15 fewer amino acids at the C terminus than SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises between about 1-10 fewer amino acids at the C terminus than SEQ ID NO: 17. In some embodiments, the reverse transcriptase comprises between about 1-5 fewer amino acids at the C terminus than SEQ ID NO: 17.Enzyme Architecture

[0102] The present disclosure features polymerases, e.g., reverse transcriptases, and fragments or variants thereof. In one aspect, the present disclosure features group II intron reverse transcriptases, e g., maturases, e.g., MarathonRT or UltraMarathonRT. Group II intron reverse transcriptases comprise an N-terminal reverse transcriptase (RT) domain and a maturase (X or thumb) domain. Group II intron reverse transcriptases may comprise a C-terminal endonuclease domain in addition to the RT domain and thumb domain. The RT domain of group II intron reverse transcriptases comprises a finger subdomain and a palm subdomain. The finger subdomain of group II intron reverse transcriptases comprises a surface of the finger (RT0)motif. The palm subdomain of group II intron reverse transcriptases comprises an insertion in the finger domain (IFD) motif. The thumb domain of group II intron reverse transcriptases comprises a DNA binding domain (DBD) subdomain. A reverse transcriptase or fragment or variant thereof described herein comprises an architecture, e.g., distinct structural regions, e.g., domains, subdomains, or motifs. In some embodiments, the reverse transcriptase comprises a domain, e.g., a reverse transcriptase (RT) domain or a thumb domain. In some embodiments, the reverse transcriptase comprises a reverse transcriptase (RT) domain, e.g., relative to any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises a reverse transcriptase (RT) domain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the RT domain comprises amino acids 1-290, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises a thumb domain. In some embodiments, the thumb domain comprises amino acids 291-427 wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the RT domain is N-terminal of the thumb domain. In some embodiments, the thumb domain is C-terminal of the RT domain.

[0103] In some embodiments, a domain within the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a subdomain. In some embodiments, the domain within the reverse transcriptase comprising a subdomain is the reverse transcriptase (RT) domain. In some embodiments, the RT domain comprises a subdomain, e.g., a finger subdomain or a palm subdomain. In some embodiments, the RT domain comprises a finger subdomain, e.g., relative to any one of SEQ ID NOs: 1-65. In some embodiments, the RT domain comprises a finger subdomain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the finger subdomain comprises amino acids 1-82, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the RT domain comprises a palm subdomain. In some embodiments, the palm subdomain comprises amino acids 83-290, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the finger subdomain is N-terminal of the palm subdomain. In someembodiments, the palm subdomain is C-terminal of the finger domain. In some embodiments, the domain within the reverse transcriptase comprising a subdomain is the thumb domain. In some embodiments, the thumb domain comprises a subdomain, e.g., a DNA binding domain (DBD) subdomain. In some embodiments, the thumb domain comprises a DBD subdomain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the DBD comprises amino acids 361-427 wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2.

[0104] In some embodiments, a domain or a subdomain within a polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a motif. In some embodiments, the domain within the reverse transcriptase comprising a motif is the RT domain. In some embodiments, the RT domain comprises a motif, e g., a surface of the finger (RTO) motif or an insertion in the finger domain (IFD) motif. In some embodiments, the RT domain comprises an RTO motif, e.g., relative to any one of SEQ ID NOs: 1-65. In some embodiments, the RT domain comprises an RTO motif, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the RTO motif comprises amino acids 5-59, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the RT domain comprises an IFD motif, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the IFD motif comprises amino acids 151-176, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the subdomain within the reverse transcriptase comprising a motif is the finger subdomain. In some embodiments, the finger subdomain comprises a motif, e.g., a surface of the finger (RTO) motif. In some embodiments, the finger subdomain comprises an RTO motif, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the subdomain within the reverse transcriptase comprising a motif is the palm subdomain. In some embodiments, the palm subdomain comprises a motif, e.g., an insertion in the finger domain (IFD) motif. In some embodiments, the palm subdomain comprises an IFD motif, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0105] A polymerase described herein, e.g., reverse transcriptase, or a fragment or variant thereof comprises a secondary structure, e.g., an alpha helix, a beta sheet, or a loop. In someembodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises an alpha helix, e.g., alpha helix al, a2, a3, a4, a5, a6, a7, a8, a9, alO, all, al2, al3, al4, al5, al6, al7, al8, or al9, e.g., relative to any one of SEQ ID NOs: 1-65. In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises an alpha helix, e.g., alpha helix al, a2, a3, a4, a5, a6, a7, a8, a9, alO, all, al2, al3, al4, al5, al6, al7, al8, or al9, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, al comprises amino acids 5-10, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, a2 comprises amino acids 13-27, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, a3 comprises amino acids 36-57, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, a4 comprises amino acids 84-104, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, a5 comprises amino acids 118-132, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, a6 comprises amino acids 145-148, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, a7 comprises amino acids 151-160, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, a8 comprises amino acids 165-178, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, a9 comprises amino acids 198-217, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, alO comprises amino acids 234-252, wherein the amino acid positions correspond to the amino acid positions in a reference sequence,e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, all comprises amino acids 292-306, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, al2 comprises amino acids 314-332, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, al3 comprises amino acids 338-360, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, al4 comprises amino acids 363-373, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, al5 comprises amino acids 376-385, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, al6 comprises amino acids 389-395, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, al 7 comprises amino acids 398-403, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, al 8 comprises amino acids 405-411, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, al 9 comprises amino acids 415-422, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2.

[0106] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a beta sheet, e.g., beta sheet 1, 02, 03, 04, 05, or 06, e.g., relative to any one of SEQ ID NOs: 1-65. In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a beta sheet, e.g., beta sheet 01, 02, 03, 04, 05, or 06, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, 01 comprises amino acids 136-141, wherein the amino acid positions correspond to the amino acid positions in areference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, 02 comprises amino acids 220-223, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, 3 comprises amino acids 227-232, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, 04 comprises amino acids 263-265, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, 05 comprises amino acids 275-279. In some embodiments, 06 comprises amino acids 286-290, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2.

[0107] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a loop, e.g., an unstructured region, e.g., LI, L2, L3, L4, L5, L6, L7, L8, L9, L10, Lil, L12, L13, L14, L15, L16, L17, L18, L19, L20, L21, L22, L23, L24, L25, or L26, e.g., relative to any one of SEQ ID NOs: 1-65. In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a loop, e.g., an unstructured region, e.g., LI, L2, L3, L4, L5, L6, L7, L8, L9, L10, Lil, L12, L13, L14, L15, L16, L17, L18, L19, L20, L21, L22, L23, L24, L25, or L26, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, LI comprises amino acids 1-4, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L2 comprises amino acids 11-12, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L3 comprises amino acids 28-35, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L4 comprises amino acids 58-83, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L5 comprises amino acids 105-117, wherein theamino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L6 comprises amino acids 133-135, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L7 comprises amino acids 142-144, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L8 comprises amino acids 149-150, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L9 comprises amino acids 161-164, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, LIO comprises amino acids 179-197, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, Lil comprises amino acids 218-219, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L12 comprises amino acids 224-226, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L13 comprises amino acids 233, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L14 comprises amino acids 253-262, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L15 comprises amino acids 266-274, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L16 comprises amino acids 280-285, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L17 comprises aminoacid 291, wherein the amino acid position corresponds to the amino acid position in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L18 comprises amino acids 307-313, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L19 comprises amino acids 333-337, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L20 comprises amino acids 361-362, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L21 comprises amino acids 374-375, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L22 comprises amino acids 386-388, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L23 comprises amino acids 396-397, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L24 comprises amino acid 404, wherein the amino acid position corresponds to the amino acid position in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L25 comprises amino acids 412-414, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, L26 comprises amino acids 423-427, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2.

[0108] In some embodiments, the domains of the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprise a secondary structure, e.g., comprise an alpha helix, a beta sheet, or a loop. In some embodiments, the domain comprising a secondary structure is the reverse transcriptase (RT) domain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the RT domain comprises an alpha helix, e.g., alpha helix al, a2, a3, a4, a5, a6,a7, a8, a9, or al O, e.g, relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the RT domain comprises a beta sheet, e.g, beta sheet 1, 02, 03, 04, 05, or 06, e.g, relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the RT domain comprises a loop, e.g., loop LI, L2, L3, L4, L5, L6, L7, L8, L9, LIO, Lil, L12, L13, L14, L15, or L16, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the domain comprising a secondary structure is the thumb domain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the thumb domain comprises an alpha helix, e.g., alpha helix all, a!2, al3, a!4, al5, al6, al7, a!8, or a!9. In some embodiments, the thumb domain comprises a loop, e.g., loop L17, L18, L19, L20, L21, L22, L23, L24, L25, or L26, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0109] In some embodiments, the subdomains of the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprise a secondary structure, e.g., comprise an alpha helix, a beta sheet, or a loop. In some embodiments, the subdomain comprising a secondary structure is the finger subdomain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the finger subdomain comprises an alpha helix, e.g., alpha helix al, a2, or a3, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the finger subdomain comprises a loop, e.g., loop LI, L2, L3, or L4, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the subdomain comprising a secondary structure is the palm subdomain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the palm subdomain comprises an alpha helix, e.g., alpha helix a4, a5, a6, a7, a8, a9, or a 10, e g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the palm subdomain comprises a loop, e.g., loop L4, L5, L6, L7, L8, L9, LIO, Lil, L12, L13, L14, L15, or L16, e.g, relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the subdomain comprising a secondary structure is the DNA binding domain (DBD) , e.g, relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the DBD comprises an alpha helix, e.g, alpha helix a!4, al 5, al6, al 7, a!8, or a!9, e.g, relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the DBD comprises a loop, e.g, loop L20, L21, L22, L23, L24, L25, or L26, e.g, relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0110] In some embodiments, the motifs of the polymerase, e.g, reverse transcriptase, or fragment or variant thereof comprise a secondary structure, e.g, comprise an alpha helix, a beta sheet, or a loop. In some embodiments, the motif comprising a secondary structure is the surface of the finger (RT0) motif, e.g, relative to SEQ ID NO: 1 or SEQ ID NO: 2. In someembodiments, the RTO motif comprises an alpha helix, e.g., alpha helix al, a2, or a3, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the RTO motif comprises a loop, e.g., loop L2, L3, or L4, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the motif comprising a secondary structure is the insertion in the finger (IFD) motif, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the IFD motif comprises an alpha helix, e.g., alpha helix a7 or a8, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the IFD motif comprises a loop, e.g., loop L9, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0111] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises an architecture shown in Table 2, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.Table 2. Reverse transcriptase architecture.

[0112] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a dimer, e.g., a complex comprising a first reverse transcriptase monomer bound to a second monomer of the same reverse transcriptase. In some embodiments, the dimer comprises a dimerization interface, e.g., an interface between the two monomers of a dimer, e.g., a region of a monomer that interacts with another monomer to form a dimer. In some embodiments, the dimerization interface is within the RT domain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the dimerization interface is within the finger subdomain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the dimerization interface within the finger subdomain comprises amino acids positions 37 and 38, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2, e.g., R37 and N38. In some embodiments, the dimerization interface is within the palm subdomain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the dimerization interface within the palm subdomain comprises amino acids positions 130, 131, 132, 133, 135, 136, 139, 204, 202, and 287, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2, e.g., C130, A131, Q132, Q133, 1135, L136, L139, V202, T204, and F287. In some embodiments, the dimerization interface is within the thumb domain. In some embodiments, the dimerization interface within the thumb domain comprises amino acid position 300, wherein the amino acid position corresponds to the amino acid position in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2, e.g., A300.

[0113] In some embodiments, the polymerase, e g., reverse transcriptase, or fragment or variant thereof comprises a nucleic acid binding region, e.g., a DNA binding region or an RNA binding region. In some embodiments, the reverse transcriptase comprises a DNA bindingregion, e.g., a region that interacts with DNA. In some embodiments, the DNA binding region is within the palm subdomain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the DNA binding region within the palm subdomain comprises amino acids positions 136, 266, 278, 279, and 281, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2, e.g., W136, R266, Y278, F279, and P281. In some embodiments, the DNA binding region is within the thumb domain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the DNA binding region within the thumb domain comprises amino acids positions 336, 337, 338, 339, 346, 347, 349, 353, 395, and 405, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2, e.g., S336, M337, K338, T339, S346, R347, R349, R353, N395, and N405. In some embodiments, the DNA binding region is within the DNA binding domain (DBD) subdomain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the DNA binding region within the DBD subdomain comprises amino acids positions 361, 378, 381, 382, 385, 386, 389, 392, 396, and 398, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2, e.g., K361, N378, R381, R382, Y385, T386, R389, Y392, K396, and A398.

[0114] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises an RNA binding region, e.g., a region that interacts with RNA. In some embodiments, the RNA binding region is within the finger subdomain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the RNA binding region within the finger subdomain comprises amino acid position 58, wherein the amino acid position corresponds to the amino acid position in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2, e.g., R58. In some embodiments, the RNA binding region is within the palm subdomain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the RNA binding region within the palm subdomain comprises amino acids positions 152, 156, 160, 217, 234, 237, 240, 243, 244, and 247, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2, e.g., D152, T156, R160, R217, S234, S237, R240, R243, N244, and R247. In some embodiments, the RNA binding region iswithin the IFD motif, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the DNA binding region within the IFD motif comprises amino acids positions 152, 156, and 160, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2, e.g., D152, T156, and R160. In some embodiments, the RNA binding region is within the thumb domain, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the RNA binding region within the thumb domain comprises amino acids positions 300, 303, 308, 309, 347, 350, 351, and 358, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2, e.g., K300, K303, R308, S309, R347, Y350, R351, and K358. In some embodiments, the RNA binding region is within the DNA binding domain (DBD) subdomain, e g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the RNA binding region within the DBD subdomain comprises amino acids positions 388, 389, 390, 391, and 395, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2, e.g., K388, R389, 1390, A391, and N395.

[0115] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises an amino acid comprising a property, e.g., charge, polarity, or hydrophobicity. In some embodiments, the reverse transcriptase comprises a positively charged amino acid, e.g., arginine (R), histidine (H), or lysine (K). In some embodiments, the reverse transcriptase comprises a negatively charged amino acid, e.g., aspartate (D) or glutamate (E). In some embodiments, the reverse transcriptase comprises a neutral amino acid, e.g., an uncharged amino acid, e.g., serine (S), threonine (T), asparagine (N), glutamine (Q), cysteine (C), glycine (G), proline (P), alanine (A), valine (V), isoleucine (I), leucine (L), methionine (M), phenylalanine (F), tyrosine (Y), or tryptophan (W). In some embodiments, the reverse transcriptase comprises a polar amino acid, e.g., serine, threonine, tyrosine, asparagine, glutamine, arginine, histidine, lysine, aspartate, or glutamate. In some embodiments, the reverse transcriptase comprises a nonpolar amino acid, e.g., glycine, alanine, valine, cysteine, proline, leucine, isoleucine, methionine, tryptophan, or phenylalanine. In some embodiments, the reverse transcriptase comprises a hydrophobic amino acid, e.g., methionine, proline, tryptophan, isoleucine, alanine, valine, leucine, or phenylalanine.

[0116] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation that changes a property at a given position in the amino acid sequence, e.g., changes the charge, polarity, or hydrophobicity at a given position in the amino acid sequence. In some embodiments, the property at a given position in the amino acid sequence that is changed by the mutation is the charge, e.g., the charge is changed from positive to negative, from positive to neutral, from negative to positive, from negative to neutral, from neutral to positive, or from neutral to negative. In some embodiments, the mutation changes the charge at a given amino acid position from positive to negative, e.g., changes an R, H, or K amino acid to a D or E amino acid. In some embodiments, the mutation changes the charge at a given amino acid position from positive to neutral, e.g., changes an R, H, or K amino acid to a T, C, Y, N, G, S, Q, M, P, W, I, A, V, L, or F amino acid. In some embodiments, the mutation changes the charge at a given amino acid position from negative to positive, e g., changes a D or E amino acid to an R, H, or K amino acid. In some embodiments, the mutation changes the charge at a given amino acid position from negative to neutral, e.g., changes a D or E amino acid to a T, C, Y, N, G, S, Q, M, P, W, I, A, V, L, or F amino acid. In some embodiments, the mutation changes the charge at a given amino acid position from neutral to positive, e.g., changes a T, C, Y, N, G, S, Q, M, P, W, I, A, V, L, or F amino acid to an R, H, or K amino acid. In some embodiments, the mutation changes the charge at a given amino acid position from neutral to negative, e.g., changes a T, C, Y, N, G, S, Q, M, P, W, I, A, V, L, or F amino acid to a D or E amino acid.

[0117] In some embodiments, the property at a given position in the amino acid sequence that is changed by the mutation is the polarity, e.g., the polarity is changed from polar to nonpolar or from nonpolar to polar. In some embodiments, the mutation changes the polarity from polar to nonpolar, e.g., changes an R, H, K, D, E, T, C, Y, N, G, S, or Q amino acid to an M, P, W, I, A, V, L, or F amino acid. In some embodiments, the mutation changes the polarity from nonpolar to polar, e.g., changes an M, P, W, I, A, V, L, or F amino acid to an R, H, K, D, E, T, C, Y, N, G, S, or Q amino acid.

[0118] In some embodiments, the property at a given position in the amino acid sequence that is changed by the mutation is the hydrophobicity, e.g., the hydrophobicity is changed from hydrophobic to non-hydrophobic or from non-hydrophobic to hydrophobic. In some embodiments, the mutation changes the hydrophobicity from hydrophobic to non-hydrophobic,e.g., changes an A, V, I, L, M, F, Y, or W amino acid to an R, H, K, D, E, S, T, N, Q, C, G, or P amino acid. In some embodiments, the mutation changes the hydrophobicity from nonhydrophobic to hydrophobic, e.g., changes an R, H, K, D, E, S, T, N, Q, C, G, or P amino acid to an A, V, I, L, M, F, Y, or W amino acid.

[0119] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation, e.g., an amino acid substitution, on the surface of the reverse transcriptase or within the hydrophobic core of the reverse transcriptase. In some embodiments, the reverse transcriptase comprises a mutation on the surface, e.g., the solvent- exposed or hydrophilic surface of the reverse transcriptase. In some embodiments, the reverse transcriptase comprises a mutation within the hydrophobic core, e.g., within the center or nonsolvent exposed region of the folded reverse transcriptase structure.

[0120] In some embodiments, the polymerase, e g., reverse transcriptase, or fragment or variant thereof comprises a mutation, e.g., an amino acid substitution, e.g., relative to a reference sequence, e.g., any one of SEQ ID NOs: 1-65. In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation, e.g., an amino acid substitution, e.g., relative to a reference sequence, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. For example, a reverse transcriptase comprising a mutation comprises an amino acid substitution at a given position in the amino acid sequence, e.g., relative to a reference sequence. In some embodiments, the reverse transcriptase comprises a mutation relative to a reference sequence, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 1. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 3. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 4. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 5. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 6. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 7. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 8. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 9. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 10. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 11. In some embodiments, the reversetranscriptase comprises a mutation relative to SEQ ID NO: 12. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 13. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 14. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 15. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 16. In some embodiments, the reverse transcriptase comprises a mutation relative to SEQ ID NO: 17.

[0121] In some embodiments, the reverse transcriptase comprises a mutation in a domain, a subdomain, a motif, or a secondary structure, e.g., relative to a reference sequence. In some embodiments, the reverse transcriptase comprises a mutation in a domain, e.g., the reverse transcriptase (RT) domain or the thumb domain, e.g., relative to any one of SEQ ID NOs: 1-65. In some embodiments, the reverse transcriptase comprises a mutation in a domain, e.g., the reverse transcriptase (RT) domain or the thumb domain, e g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the reverse transcriptase comprises a mutation in the RT domain, e.g., a mutation comprising an amino acid position selected from amino acid positions 1-290, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., relative to any one of SEQ ID NOs: 1-2 or 6-17. In some embodiments, the reverse transcriptase comprises a mutation in the RT domain, e.g., a mutation comprising an amino acid position selected from amino acid positions 1-290, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., relative to SEQ ID NO:1 or SEQ ID NO:2. In some embodiments, the mutation in the RT domain comprises an amino acid position selected from amino acid positions 58, 59, 160, 240, 243, 247, 266, and 289, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the RT domain comprises an amino acid position selected from amino acid positions 58, 59, 160, 240, 243, 247, 266, 282, and 289, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the mutation in the RT domain comprises a mutation selected from R58X, K59X, R160X, R240X, R243X, R247X, R266X, and K289X, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the RTdomain comprises a mutation selected from R58X, K59X, R160X, R240X, R243X, R247X, R266X, R282X, and K289X, wherein X denotes any amino acid, e.g., relative to any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the mutation in the RT domain comprises a mutation selected from R58Q, R58K, K59S, K59T, K59N, K59Q, K59D, K59E, K59A, R160S, R160T, R160N, R160Q, R160D, R160E, R160A, R240S, R240T, R240N, R240Q, R240D, R240E, R240A, R243S, R243T, R243N, R243Q, R243D, R243E, R243A, R247S, R247T, R247N, R247Q, R247D, R247E, R247A, R266S, R266T, R266N, R266Q, R266D, R266E, R266A, K289S, K289T, K289N, K289Q, K289D, K289E, and K289A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the RT domain comprises a mutation selected from R58Q, R58K, K59S, K59T, K59N, K59Q, K59D, K59E, K59A, R160S, R160T, R160N, R160Q, R160D, R160E, R160A, R240S, R240T, R240N, R240Q, R240D, R240E, R240A, R243S, R243T, R243N, R243Q, R243D, R243E, R243A, R247S, R247T, R247N, R247Q, R247D, R247E, R247A, R266S, R266T, R266N, R266Q, R266D, R266E, R266A, R282E, R282D, R282S, R282T, R282N, R282Q, R282A, K289S, K289T, K289N, K289Q, K289D, K289E, and K289A, e.g., relative to any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the RT domain comprises an amino acid selected from Q58, K58, S59, T59, N59, Q59, D59, E59, A59, S160, T160, N160, Q160, D160, E160, A160, S240, T240, N240, Q240, D240, E240, A240, S243, T243, N243, Q243, D243, E243, A243, S247, T247, N247, Q247, D247, E247, A247, S266, T266, N266, Q266, D266, E266, A266, S289, T289, N289, Q289, D289, E289, and A289, e g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the RT domain comprises an amino acid selected from Q58, K58, S59, T59, N59, Q59, D59, E59, A59, S160, T160, N160, Q160, D160, E160, A160, S240, T240, N240, Q240, D240, E240, A240, S243, T243, N243, Q243, D243, E243, A243, S247, T247, N247, Q247, D247, E247, A247, S266, T266, N266, Q266, D266, E266, A266, E282, D282, S282, T282, N282, Q282, A282, S289, T289, N289, Q289, D289, E289, and A289, e.g., relative to any one of SEQ ID NOs: 1-2 and 6-17.

[0122] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in the thumb domain, e.g., a mutation comprising an amino acid position selected from amino acid positions 291-427, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., any one of SEQ ID NOs: 1-2 or 6-17. In some embodiments, thepolymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in the thumb domain, e.g., a mutation comprising an amino acid position selected from amino acid positions 291-427, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the thumb domain comprises an amino acid position selected from amino acid positions 303, 338, 342, 347, 349, 351, 358, 361, 381, 382, 388, 389, and 396, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the thumb domain comprises an amino acid position selected from amino acid positions 293, 303, 308, 338, 342, 347, 349, 351, 358, 361, 381, 382, 388, 389, and 396, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e g., any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the mutation in the thumb domain comprises a mutation selected from K303X, K338X, K342X, R347X, R349X, R351X, K358X, K361X, R381X, R382X, K388X, R389X, and K396X, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the thumb domain comprises a mutation selected from K293X, K303X, R308X, K338X, K342X, R347X, R349X, R351X, K358X, K361X, R381X, R382X, K388X, R389X, and K396X, wherein X denotes any amino acid, e.g., relative to any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the mutation in the thumb domain comprises a mutation selected from K303S, K303T, K303N, K303Q, K303D, K303E, K303A, K338S, K338T, K338N, K338Q, K338D, K338E, K338A, K342S, K342T, K342N, K342Q, K342D, K342E, K342A, R347S, R347T, R347N, R347Q, R347D, R347E, R347A, R349T, R349Q, R349E, R349A, R351T, R351Q, R351N, R351D, R351E, R351S, R351A, K358S, K358T, K358N, K358Q, K358D, K358E, K358A, K361S, K361T, K361N, K361Q, K361D, K361E, K361A, R381T, R381Q, R381N, R382S, R382T, R382N, R382Q, R382D, R382E, R382A, K388S, K388T, K388N, K388Q, K388D, K388E, K388A, R389S, R389T, R389N, R389Q, R389D, R389E, R389A, K396S, K396T, K396N, K396Q, K396D, K396E, and K396A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the thumb domain comprises a mutation selected from K293Q, K293R, K293H, K293D, K293E, K293N, K293S, K293T, K293A, K3O3S, K303T, K303N, K303Q, K303D, K303E, K3O3A, R308E, R308D, R308N, R308Q, R308S, R308T,R308A, K338S, K338T, K338N, K338Q, K338D, K338E, K338A, K342S, K342T, K342N, K342Q, K342D, K342E, K342A, R347S, R347T, R347N, R347Q, R347D, R347E, R347A, R349T, R349Q, R349E, R349A, R351T, R351Q, R351N, R351D, R351E, R351S, R351A, K358S, K358T, K358N, K358Q, K358D, K358E, K358A, K361S, K361T, K361N, K361Q, K361D, K361E, K361A, R381T, R381Q, R381N, R382S, R382T, R382N, R382Q, R382D, R382E, R382A, K388S, K388T, K388N, K388Q, K388D, K388E, K388A, R389S, R389T, R389N, R389Q, R389D, R389E, R389A, K396S, K396T, K396N, K396Q, K396D, K396E, and K396A, e.g., relative to any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the thumb domain comprises an amino acid selected from S303, T303, N303, Q303, D303, E303, A303, S338, T338, N338, Q338, D338, E338, A338, S342, T342, N342, Q342, D342, E342, A342, S347, T347, N347, Q347, D347, E347, A347, T349, Q349, E349, A349, T351, Q351, N351, D351, E351, S351, A351, S358, T358, N358, Q358, D358, E358, A358, S361, T361, N361, Q361, D361, E361, A361, T381, Q381, N381, S382, T382, N382, Q382, D382, E382, A382,5388, T388, N388, Q388, D388, E388, A388, S389, T389, N389, Q389, D389, E389, A389, S396, T396, N396, Q396, D396, E396, and A396, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the thumb domain comprises an amino acid selected from Q293, R293, H293, D293, E293, N293, S293, T293, A293, S303, T3O3, N303, Q303, D303, E303, A303, E308, D308, N308, Q308, S308, T308, A308, S338, T338, N338, Q338, D338, E338, A338, S342, T342, N342, Q342, D342, E342, A342, S347, T347, N347, Q347, D347, E347, A347, T349, Q349, E349, A349, T351, Q351, N351, D351, E351, S351, A351, S358, T358, N358, Q358, D358, E358, A358, S361, T361, N361, Q361, D361, E361, A361, T381, Q381, N381, S382, T382, N382, Q382, D382, E382, A382, S388, T388, N388, Q388, D388, E388, A388,5389, T389, N389, Q389, D389, E389, A389, S396, T396, N396, Q396, D396, E396, and A396, e.g., relative to any one of SEQ ID NOs: 1-2 and 6-17.

[0123] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in a subdomain, e.g., the finger subdomain, the palm subdomain, or the DNA binding domain (DBD) subdomain, e.g., any one of SEQ ID NOs: 1-2 or 6-17. In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in a subdomain, e.g., the finger subdomain, the palm subdomain, or the DNA binding domain (DBD) subdomain, e.g., SEQ ID NO:1 or SEQ ID NO:2. In some embodiments, the reverse transcriptase comprises a mutation in the finger subdomain, e.g., amutation comprising an amino acid position selected from amino acid positions 1-82, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the finger subdomain comprises an amino acid position selected from amino acid positions 58 and 59, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the finger subdomain comprises a mutation selected from R58X and K59X, wherein X denotes any amino acid, e g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the finger subdomain comprises a mutation selected from R58Q, R58K, K59S, K59T, K59N, K59Q, K59D, K59E, and K59A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the finger subdomain comprises an amino acid selected from Q58, K58, S59, T59, N59, Q59, D59, E59, and A59, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0124] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in the palm subdomain, e.g., a mutation comprising an amino acid position selected from amino acid positions 83-290, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., any one of SEQ ID NOs: 1-2 or 6-17. In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in the palm subdomain, e.g., a mutation comprising an amino acid position selected from amino acid positions 83-290, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO:2. In some embodiments, the mutation in the palm subdomain comprises an amino acid position selected from amino acid positions 160, 240, 243, 247, 266, and 289, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the palm subdomain comprises an amino acid position selected from amino acid positions 160, 240, 243, 247, 266, 282, and 289, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the mutation in the palm subdomain comprises a mutation selected from R160X, R240X, R243X, R247X, R266X,and K289X, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the palm subdomain comprises a mutation selected from R160X, R240X, R243X, R247X, R266X, R282X, and K289X, wherein X denotes any amino acid, e.g., relative to any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the mutation in the palm subdomain comprises a mutation selected from R160S, R160T, R160N, R160Q, R160D, R160E, R160A, R240S, R240T, R240N, R240Q, R240D, R240E, R240A, R243S, R243T, R243N, R243Q, R243D, R243E, R243A, R247S, R247T, R247N, R247Q, R247D, R247E, R247A, R266S, R266T, R266N, R266Q, R266D, R266E, R266A, K289S, K289T, K289N, K289Q, K289D, K289E, and K289A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the palm subdomain comprises a mutation selected from R160S, R160T, R160N, R160Q, R160D, R160E, R160A, R240S, R240T, R240N, R240Q, R240D, R240E, R240A, R243S, R243T, R243N, R243Q, R243D, R243E, R243A, R247S, R247T, R247N, R247Q, R247D, R247E, R247A, R266S, R266T, R266N, R266Q, R266D, R266E, R266A, R282E, R282D, R282S, R282T, R282N, R282Q, R282A, K289S, K289T, K289N, K289Q, K289D, K289E, and K289A, e.g., relative to any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the palm subdomain comprises an amino acid selected from SI 60, T160, N160, Q160, D160, E160, A160, S240, T240, N240, Q240, D240, E240, A240, S243, T243, N243, Q243, D243, E243, A243, S247, T247, N247, Q247, D247, E247, A247, S266, T266, N266, Q266, D266, E266, A266, S289, T289, N289, Q289, D289, E289, and A289, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the palm subdomain comprises an amino acid selected from S160, T160, N160, Q160, D160, E160, A160, S240, T240, N240, Q240, D240, E240, A240, S243, T243, N243, Q243, D243, E243, A243, S247, T247, N247, Q247, D247, E247, A247, S266, T266, N266, Q266, D266, E266, A266, E282, D282, S282, T282, N282, Q282, A282, S289, T289, N289, Q289, D289, E289, and A289, e.g., relative to any one of SEQ ID NOs: 1-2 and 6-17.

[0125] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in the DNA binding domain (DBD) subdomain, e.g., a mutation comprising an amino acid position selected from amino acid positions 361-427, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., any one of SEQ ID NOs: 1-2 or 6-17. In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereofcomprises a mutation in the DNA binding domain (DBD) subdomain, e.g., a mutation comprising an amino acid position selected from amino acid positions 361-427, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO:1 or SEQ ID NO:2. In some embodiments, the mutation in the DBD subdomain comprises an amino acid position selected from amino acid positions 361, 381, 382, 388, 389, and 396, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the DBD subdomain comprises a mutation selected from K361X, R381X, R382X, K388X, R389X, and K396X, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the DBD subdomain comprises a mutation selected from K361S, K361T, K361N, K361Q, K361D, K361E, K361A, R381T, R381Q, R381N, R382S, R382T, R382N, R382Q, R382D, R382E, R382A, K388S, K388T, K388N, K388Q, K388D, K388E, K388A, R389S, R389T, R389N, R389Q, R389D, R389E, R389A, K396S, K396T, K396N, K396Q, K396D, K396E, and K396A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the DBD subdomain comprises an amino acid selected from S361, T361, N361, Q361, D361, E361, A361, T381, Q381, N381, S382, T382, N382, Q382, D382, E382, A382, S388, T388, N388, Q388, D388, E388, A388, S389, T389, N389, Q389, D389, E389, A389, S396, T396, N396, Q396, D396, E396, and A396, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0126] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in a motif, e.g., the surface of the finger (RTO) motif or the insertion in the finger domain (IFD) motif, e.g., relative to any one of SEQ ID NOs: 1-2 or 6-17. In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in a motif, e.g., the surface of the finger (RTO) motif or the insertion in the finger domain (IFD) motif, e.g., relative to SEQ ID NO: 1 or SEQ ID NO:2. In some embodiments, the reverse transcriptase comprises a mutation in the RTO motif, e g., a mutation comprising an amino acid position selected from amino acid positions 5-59, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the RTO motif comprises an amino acid position selected from amino acidpositions 58 and 59, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g, a reverse transcriptase amino acid sequence, e.g, SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the RTO motif comprises a mutation selected from R58X and K59X, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the RTO motif comprises a mutation selected from R58Q, R58K, K59S, K59T, K59N, K59Q, K59D, K59E, and K59A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the RTO motif comprises an amino acid selected from Q58, K58, S59, T59, N59, Q59, D59, E59, and A59, e.g, relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0127] In some embodiments, the polymerase, e.g, reverse transcriptase, or fragment or variant thereof comprises a mutation in the IFD motif, e.g, a mutation comprising an amino acid position selected from amino acid positions 151-176, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g, a reverse transcriptase amino acid sequence, e.g, any one of SEQ ID NOs: 1-2 or 6-17. In some embodiments, the polymerase, e.g, reverse transcriptase, or fragment or variant thereof comprises a mutation in the IFD motif, e.g, a mutation comprising an amino acid position selected from amino acid positions 151-176, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g, a reverse transcriptase amino acid sequence, e.g, SEQ ID NO: 1 or SEQ ID NO:2. In some embodiments, the mutation in the IFD motif comprises amino acid position 160, wherein the amino acid position corresponds to the amino acid position in a reference sequence, e.g, a reverse transcriptase amino acid sequence, e.g, SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the IFD motif comprises an R160X mutation, wherein X denotes any amino acid, e.g, relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in the IFD motif comprises a mutation selected from R160S, R160T, R160N, R160Q, R160D, R160E, and R160A, e.g, relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the IFD motif comprises an amino acid selected from SI 60, T160, N160, QI 60, D160, E160, and A160, e.g, relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0128] In some embodiments, the polymerase, e.g, reverse transcriptase, or fragment or variant thereof comprises a mutation in a secondary structure, e.g, in an alpha helix, a beta sheet, or a loop. In some embodiments, the reverse transcriptase comprises a mutation in an alpha helix, e g, a mutation in alpha helix al, a2, a3, a4, a5, a6, a7, a8, a9, alO, all, a!2, a!3, a!4, a!5,al 6, al 7, al 8, or al 9, e.g., relative to any one of SEQ ID NOs: 1-65. In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in a secondary structure, e.g., in an alpha helix, a beta sheet, or a loop. In some embodiments, the reverse transcriptase comprises a mutation in an alpha helix, e.g., a mutation in alpha helix al, a2, a3, a4, a5, a6, a7, a8, a9, alO, all, al2, al3, al4, al5, al6, al7, al8, or al9, e.g., relative to SEQ ID NO: 1 or SEQ ID NO:2. In some embodiments, the reverse transcriptase comprises a mutation in a7, e.g., a mutation comprising an amino acid position selected from amino acid positions 151-160, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in a7 comprises amino acid position 160, wherein the amino acid position corresponds to the amino acid position in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in a7 comprises an R160X mutation, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in a 7 comprises a mutation selected from R160S, R160T, R160N, R160Q, R160D, R160E, and R160A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, a7 comprises an amino acid selected from S160, T160, N160, Q160, D160, E160, and A160, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0129] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in alO, e.g., a mutation comprising an amino acid position selected from amino acid positions 234-252, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., any one of SEQ ID NOs: 1-2 or 6-17. In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in alO, e.g., a mutation comprising an amino acid position selected from amino acid positions 234-252, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO:2. In In some embodiments, the mutation in alO comprises an amino acid position selected from amino acid positions 240, 243, and 247, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in alO comprises a mutationselected from R240X, R243X, and R247X, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in alO comprises a mutation selected from R240S, R240T, R240N, R240Q, R240D, R240E, R240A, R243S, R243T, R243N, R243Q, R243D, R243E, R243A, R247S, R247T, R247N, R247Q, R247D, R247E, and R247A. In some embodiments, alO comprises an amino acid selected from S240, T240, N240, Q240, D240, E240, A240, S243, T243, N243, Q243, D243, E243, A243, S247, T247, N247, Q247, D247, E247, and A247, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0130] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in al 1, e.g., a mutation comprising an amino acid position selected from amino acid positions 292-306, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e g., any one of SEQ ID NOs: 1-2 or 6-17. In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in all, e g., a mutation comprising an amino acid position selected from amino acid positions 292-306, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO:2. In some embodiments, the mutation in al l comprises amino acid position 303, wherein the amino acid position corresponds to the amino acid position in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in al l comprises amino acid position 293 or 303, wherein the amino acid position corresponds to the amino acid position in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the mutation in all comprises a K303X mutation, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in all comprises a K293X or K303X mutation, wherein X denotes any amino acid, e.g., relative to any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, the mutation in all comprises a mutation selected from K303S, K303T, K303N, K303Q, K303D, K303E, and K303A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in al l comprises a mutation selected from K293Q, K293R, K293H, K293D, K293E, K293N, K293S, K293T, K293A, K3O3S, K303T, K303N, K303Q, K303D, K303E, and K303A, e.g., relative to any one of SEQ ID NOs: 1-2 and 6-17. In some embodiments, all comprises an amino acid selected from S303, T303, N303,Q303, D3O3, E303, and A303, e g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, all comprises an amino acid selected from Q293, R293, H293, D293, E293, N293, S293, T293, A293, S303, T3O3, N303, Q303, D303, E303, and A303, e.g., relative to any one of SEQ ID NOs: 1-2 or 6-17.

[0131] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in al3, e.g., a mutation comprising an amino acid position selected from amino acid positions 338-360, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., any one of SEQ ID NOs: 1-2 or 6-17. In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in al3, e.g., a mutation comprising an amino acid position selected from amino acid positions 338-360, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO:2. In some embodiments, the mutation in al3 comprises an amino acid position selected from amino acid positions 338, 342, 347, 349, 351, and 358, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in al3 comprises a mutation selected from K338X, K342X, R347X, R349X, R351X, and K358X, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in al3 comprises a mutation selected from K338S, K338T, K338N, K338Q, K338D, K338E, K338A, K342S, K342T, K342N, K342Q, K342D, K342E, K342A, R347S, R347T, R347N, R347Q, R347D, R347E, R347A, R349T, R349Q, R349E, R349A, R351T, R351Q, R351N, R351D, R351E, R351S, R351A, K358S, K358T, K358N, K358Q, K358D, K358E, and K358A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, a!3 comprises an amino acid selected from S338, T338, N338, Q338, D338, E338, A338, S342, T342, N342, Q342, D342, E342, A342, S347, T347, N347, Q347, D347, E347, A347, T349, Q349, E349, A349, T351, Q351, N351, D351, E351, S351, A351, S358, T358, N358, Q358, D358, E358, and A358, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0132] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in al5, e.g., a mutation comprising an amino acid position selected from amino acid positions 376-385, wherein the amino acid positions correspond to theamino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., any one of SEQ ID NOs: 1-2 or 6-17. In some embodiments, the polymerase, e g., reverse transcriptase, or fragment or variant thereof comprises a mutation in al5, e.g., a mutation comprising an amino acid position selected from amino acid positions 376-385, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO:2. In some embodiments, the mutation in al 5 comprises an amino acid position selected from amino acid positions 381 and 382, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in al 5 comprises a mutation selected from R381X and R382X, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in al 5 comprises a mutation selected from R381T, R381Q, R381N, R382S, R382T, R382N, R382Q, R382D, R382E, and R382A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, al 5 comprises an amino acid selected from T381, Q381, N381, S382, T382, N382, Q382, D382, E382, and A382, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

[0133] In some embodiments, the polymerase, e.g., reverse transcriptase, or fragment or variant thereof comprises a mutation in al6, e.g., a mutation comprising an amino acid position selected from amino acid positions 389-395, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., any one of SEQ ID NOs: 1-2 or 6-17. In some embodiments, the polymerase, e g., reverse transcriptase, or fragment or variant thereof comprises a mutation in al6, e.g., a mutation comprising an amino acid position selected from amino acid positions 389-395, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO:2. In some embodiments, the mutation in al 6 comprises amino acid position 389, wherein the amino acid position corresponds to the amino acid positions in a reference sequence, e.g., a reverse transcriptase amino acid sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in al6 comprises a R389X mutation, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2. In some embodiments, the mutation in al6 comprises a mutation selected from R389...

Claims

CLAIMS1. A reverse transcriptase that comprises a mutation relative to a reference sequence in at least one of the following domains:(i) the reverse transcriptase (RT) domain (e.g., the finger subdomain (e.g., the RTO motif) or the palm subdomain (e.g., the insertion in the finger domain (IFD) motif));(ii) the thumb domain (e.g., the DNA binding domain (DBD) subdomain).

2. The reverse transcriptase of claim 1, wherein the reference sequence comprises a group II intron reverse transcriptase amino acid sequence, e.g., MarathonRT or UltraMarathonRT amino acid sequence, e.g., a sequence of SEQ ID NO: 1 or SEQ ID NO: 2, or a fragment or variant thereof.

3. The reverse transcriptase of claim 1, wherein the mutation is a positively charged, negatively charged, or neutral mutation.

4. The reverse transcriptase of claim 1, wherein the mutation is at an arginine residue.

5. The reverse transcriptase of claim 1, wherein the mutation is at a lysine residue.

6. The reverse transcriptase of any one of the preceding claims, wherein the mutation is within an alpha helix, a beta sheet, or a loop.

7. The reverse transcriptase of claim 1, wherein the mutation is within an alpha helix, e.g., a7, alO, al l, a!3, a!5, or al6, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

8. The reverse transcriptase of claim 1, wherein the mutation is within a beta sheet, e.g., P6, e g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

9. The reverse transcriptase of claim 1, wherein the mutation is within a loop, e.g., L4, LI 5, L16, L18, L20, L22, or L23, e g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

10. The reverse transcriptase of claim 1, wherein the mutation comprises an amino acid position selected from amino acid positions 58, 59, 160, 240, 243, 247, 266, 282, 289, 293, 303, 308, 338, 342, 347, 349, 351, 358, 361, 381, 382, 388, 389, and 396, wherein the amino acid positions correspond to the amino acid positions in a reference sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2.

11. The reverse transcriptase of claim 1, wherein the mutation is selected from R58X, K59X, R160X, R240X, R243X, R247X, R266X, R282X, K289X, K293X, K303X, R308X, K338X, K342X, R347X, R349X, R351X, K358X, K361X, R381X, R382X, K388X, R389X, and K396X, wherein X denotes any amino acid, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

12. The reverse transcriptase of claim 1, wherein the mutation is selected from R58Q, R58K, K59S, K59T, K59N, K59Q, K59D, K59E, K59A, R160S, R160T, R160N, R160Q, R160D, R160E, R160A, R240S, R240T, R240N, R240Q, R240D, R240E, R240A, R243S, R243T, R243N, R243Q, R243D, R243E, R243A, R247S, R247T, R247N, R247Q, R247D, R247E, R247A, R266S, R266T, R266N, R266Q, R266D, R266E, R266A, R282E, R282D, R282S, R282T, R282N, R282Q, R282A, K289S, K289T, K289N, K289Q, K289D, K289E, K289A, K293Q, K293R, K293H, K293D, K293E, K293N, K293S, K293T, K293A, K3O3S, K303T, K303N, K303Q, K303D, K303E, K3O3A, R308E, R308D, R308N, R308Q, R308S, R308T, R308A, K338S, K338T, K338N, K338Q, K338D, K338E, K338A, K342S, K342T, K342N, K342Q, K342D, K342E, K342A, R347S, R347T, R347N, R347Q, R347D, R347E, R347A, R349T, R349Q, R349E, R349A, R351T, R351Q, R351N, R351D, R351E, R351S, R351A, K358S, K358T, K358N, K358Q, K358D, K358E, K358A, K361S, K361T, K361N, K361Q, K361D, K361E, K361A, R381T, R381Q, R381N, R382S, R382T, R382N, R382Q, R382D, R382E, R382A, K388S, K388T, K388N, K388Q, K388D, K388E, K388A, R389S, R389T, R389N, R389Q, R389D, R389E, R389A, K396S, K396T, K396N, K396Q, K396D, K396E, and K396A, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

13. The reverse transcriptase of claim 1, wherein the mutation is in the RT domain, e.g., comprises any of amino acids 1-290, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

14. The reverse transcriptase of claim 1, wherein the mutation is in the finger subdomain, e.g., comprises any of amino acids 1-82, e.g., relative to SEQ ID NO; 1 or SEQ ID NO: 2.

15. The reverse transcriptase of claim 1, wherein the mutation is in the RTO motif, e g., comprises any of amino acids 5-59, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

16. The reverse transcriptase of claim 1, wherein the mutation is in the palm subdomain, e.g., comprises any of amino acids 83-290, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

17. The reverse transcriptase of claim 1, wherein the mutation is in the insertion in the finger domain (IFD) motif, e.g., comprises any of amino acids 151-176, e g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

18. The reverse transcriptase of claim 1, wherein the insertion is in the thumb domain, e.g., comprises any of amino acids 291-427, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

19. The reverse transcriptase of claim 1, wherein the mutation is in the DNA binding domain (DBD) subdomain, e.g., comprises any of amino acids 361-427, e g., relative to SEQ ID NO: 1 or SEQ ID NO:

220. A reverse transcriptase comprising the following domains:(i) the reverse transcriptase (RT) domain (e.g., finger subdomain (e.g., the RTO motif) or the palm subdomain (e.g., the insertion in the finger domain (IFD) motif));(ii) the thumb domain (e.g., the DNA binding domain (DBD) subdomain); and wherein the reverse transcriptase comprises one or more of the following amino acids: Q58, K58, S59, T59, N59, Q59, D59, E59, A59, S160, T160, N160, Q160, D160, E160, A160, S240, T240, N240, Q240, D240, E240, A240, S243, T243, N243, Q243, D243, E243, A243, S247, T247, N247, Q247, D247, E247, A247, S266, T266, N266, Q266, D266, E266, A266, E282, D282, S282, T282, N282, Q282, A282, S289, T289, N289, Q289, D289, E289, A289, Q293, R293, H293, D293, E293, N293, S293, T293, A293, S303, T303, N303, Q303, D303, E303,A303, E308, D308, N308, Q308, S308, T308, A308, S338, T338, N338, Q338, D338, E338, A338, S342, T342, N342, Q342, D342, E342, A342, S347, T347, N347, Q347, D347, E347, A347, T349, Q349, E349, A349, T351, Q351, N351, D351, E351, S351, A351, S358, T358, N358, Q358, D358, E358, A358, S361, T361, N361, Q361, D361, E361, A361, T381, Q381, N381, S382, T382, N382, Q382, D382, E382, A382, S388, T388, N388, Q388, D388, E388, A388, S389, T389, N389, Q389, D389, E389, A389, S396, T396, N396, Q396, D396, E396, and A396, relative to a reference sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2.

21. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises one or more of the following amino acids in the RT domain (e.g., finger subdomain (e.g., the RTO motif) or the palm subdomain (e.g., the insertion in the finger domain (IFD) motif)): Q58, K58, S59, T59, N59, Q59, D59, E59, A59, S160, T160, N160, Q160, D160, E160, A160, S240, T240, N240, Q240, D240, E240, A240, S243, T243, N243, Q243, D243, E243, A243, S247, T247, N247, Q247, D247, E247, A247, S266, T266, N266, Q266, D266, E266, A266, E282, D282, S282, T282, N282, Q282, A282, S289, T289, N289, Q289, D289, E289, and A289, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

22. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises one or more of the following amino acids in the finger subdomain (e.g., the RTO motif): Q58, K58, S59, T59, N59, Q59, D59, E59, and A59, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

23. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises one or more of the following amino acids in the palm subdomain (e.g., the insertion in the finger domain (IFD) motif), a7, alO, L15, or 6): S160, T160, N160, Q160, D160, E160, A160, S240, T240, N240, Q240, D240, E240, A240, S243, T243, N243, Q243, D243, E243, A243, S247, T247, N247, Q247, D247, E247, A247, S266, T266, N266, Q266, D266, E266, A266, E282, D282, S282, T282, N282, Q282, A282, S289, T289, N289, Q289, D289, E289, and A289, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

24. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises one or more of the following amino acids in the thumb domain (e.g., the DNA binding domain (DBD)subdomain, al l, LI 8, al 3, L20, al 5, L22, al 6, or L23): Q293, R293, H293, D293, E293, N293, S293, T293, A293, S303, T303, N3O3, Q303, D303, E3O3, A303, E308, D308, N308, Q308, S308, T308, A308, S338, T338, N338, Q338, D338, E338, A338, S342, T342, N342, Q342, D342, E342, A342, S347, T347, N347, Q347, D347, E347, A347, T349, Q349, E349, A349, T351, Q351, N351, D351, E351, S351, A351, S358, T358, N358, Q358, D358, E358, A358, S361, T361, N361, Q361, D361, E361, A361, T381, Q381, N381, S382, T382, N382, Q382, D382, E382, A382, S388, T388, N388, Q388, D388, E388, A388, S389, T389, N389, Q389, D389, E389, A389, S396, T396, N396, Q396, D396, E396, and A396, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

25. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises one or more of the following amino acids in the DNA binding domain (DBD) subdomain (e g., L20, al5, L22, al6, or L23): S361, T361, N361, Q361, D361, E361, A361, T381, Q381, N381, S382, T382, N382, Q382, D382, E382, A382, S388, T388, N388, Q388, D388, E388, A388, S389, T389, N389, Q389, D389, E389, A389, S396, T396, N396, Q396, D396, E396, and A396, e.g., relative to SEQ ID NO: 1 or SEQ ID NO: 2.

26. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises at least one mutation, e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, or more mutations, e.g., relative to any one of SEQ ID NOs: 1-65.

27. The reverse transcriptase of claim 20, wherein the reverse transcriptase has at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 99.9% sequence identity to any one of SEQ ID NOs: 1-65.

28. The reverse transcriptase of claim 20, wherein the mutation is at the interface between reverse transcriptase dimers, e.g., relative to any one of SEQ ID NOs: 1-65.

29. The reverse transcriptase of claim 20, wherein the mutation is within a binding region, e.g., a DNA or RNA binding region, e.g., relative to any one of SEQ ID NOs: 1-65.

30. The reverse transcriptase of claim 20, wherein the mutation is within a DNA binding region, e.g., relative to any one of SEQ ID NOs: 1-65.

31. The reverse transcriptase of claim 20, wherein the mutation is within an RNA binding region, e.g., relative to any one of SEQ ID NOs: 1-65.

32. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises at least two mutations relative to a reference sequence, e.g., SEQ ID NO: 1 or SEQ ID NO: 2.

33. The reverse transcriptase of claim 20, the reverse transcriptase comprises a mutation in the RT domain and a mutation in the thumb domain.

34. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises a mutation in the palm subdomain and the thumb domain.

35. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises a mutation at each of amino acid positions:(i) 58 and 59;(ii) 243, 247, and 240;(iii) 282, 338, and 342;(iv) 303, 308, and 347;(v) 338 and 342;(vi) 303 and 308;(vii) 382, 388, and 389; or(viii) 361 and 388, wherein the amino acid positions correspond to an amino acid position in a reference sequence, e g., SEQ ID NO: 1 or SEQ ID NO: 2.

36. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises mutations selected from:(i) R58X and K59X;(ii) R243X, R247X, and R240X;(iii) R282X, K338X, and K342X;(iv) K303X, R308X, and R347X;(v) K338X and K342X;(vi) K303X and R308X;(vii) R382X, K388X, and R389X; and(viii) K361X and K388X, wherein X denotes any amino acid, and wherein the amino acid positions correspond to an amino acid position in a reference sequence, e ., SEQ ID NO: 1 or SEQ ID NO: 2.

37. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises R58Q and K59E mutations, relative to SEQ ID NO: 1.

38. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises R58Q and K59S mutations, relative to SEQ ID NO: 1.

39. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises an R160Q mutation, relative to SEQ ID NO: 1.

40. The reverse transcriptase of any one of the preceding claims, wherein the reverse transcriptase comprises R243S, R247A, and R240S mutations, relative to SEQ ID NO: 1.

41. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises an R282E mutation, relative to SEQ ID NO: 1.

42. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises a K293Q mutation, relative to SEQ ID NO: 1.

43. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises R282E, K338E, and K342E mutations, relative to SEQ ID NO: 1.

44. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises K303E, R308E, and R347Q mutations, relative to SEQ ID NO: 1.

45. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises K338E and K342E mutations, relative to SEQ ID NO: 1.

46. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises K303E and R308E mutations, relative to SEQ ID NO: 1.

47. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises R382Q, K388E, and R389E mutations, relative to SEQ ID NO: 1.

48. The reverse transcriptase of any one of the preceding claims, wherein the reverse transcriptase comprises K361S and K388E mutations, relative to SEQ ID NO: 1.

49. The reverse transcriptase of claim 20, wherein the reverse transcriptase comprises any one of SEQ ID NOs: 6-17, or a sequence with about 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5%, 99.9%, or greater identity to any one of SEQ ID NOs: 6-17.

50. The reverse transcriptase of any one of the preceding claims, wherein the reverse transcriptase is a template-switching reverse transcriptase.

51. A method of performing reverse transcription comprising contacting a target RNA with the reverse transcriptase of any one of the preceding claims.

52. A method for acquiring a value for the presence of a target ribonucleic acid (RNA) in a mixture, comprising contacting the mixture with:(i) the reverse transcriptase of any one of the preceding claims;(ii) an oligonucleotide primer; and(iii) a deoxynucleotide triphosphate (dNTP) solution;thereby acquiring a value for the presence of the target RNA.

53. A method for synthesizing complementary DNA (cDNA) from a ribonucleic acid (RNA), e.g., a target RNA, in a mixture, comprising contacting the mixture with:(i) the reverse transcriptase of any one of the preceding claims;(ii) an oligonucleotide primer; and(iii) a deoxynucleotide triphosphate (dNTP) solution; thereby synthesizing cDNA.

54. A method of producing a complementary DNA (cDNA) library comprising cDNAs comprising sequences complementary to a plurality of target RNAs comprising contacting a plurality of target RNAs with:(i) a reverse transcription primer;(ii) a deoxyribonucleotide triphosphate (dNTP) solution; and(iii) the reverse transcriptase of any one of the preceding claims; thereby producing a cDNA library comprising sequences complementary to a plurality of target RNAs.

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