content: <HTML>
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  <TITLE>sv8</TITLE>
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  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  <DIV style="font-family: 'Times New Roman',Times,serif">
  
  
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>As
  filed with the Securities and Exchange Commission on August&nbsp;11,
  2005</B>
  </DIV>
  
  
  <DIV align="right" style="font-size: 10pt; margin-top: 0pt"><b>Registration
  No.&nbsp;333-_____</B>
  </DIV>
  
  
  <DIV style="width: 100%; border-bottom: 2pt solid black; font-size: 1pt">&nbsp;</DIV>
  <DIV style="width: 100%; border-bottom: 1pt solid black; font-size: 1pt">&nbsp;</DIV>
  
  
  
  
  <DIV align="center" style="font-size: 14pt; margin-top: 12pt"><B>UNITED STATES<BR>
  SECURITIES AND EXCHANGE COMMISSION</B>
  </DIV>
  
  <DIV align="center" style="font-size: 12pt"><B>WASHINGTON, D.C. 20549</B>
  </DIV>
  
  <DIV align="center" style="font-size: 18pt; margin-top: 12pt"><B>FORM S-8</B>
  </DIV>
  
  
  <DIV align="center" style="font-size: 12pt; margin-top: 12pt"><B>REGISTRATION STATEMENT UNDER<BR>
  THE SECURITIES ACT OF 1933</B>
  </DIV>
  
  <DIV align="center" style="font-size: 24pt; margin-top: 12pt"><B>Alnylam Pharmaceuticals, Inc.</B>
  </DIV>
  
  
  <DIV align="center" style="font-size: 10pt; margin-top: 0pt">(Exact Name of Registrant as Specified in Its Charter)
  </DIV>
  
  <DIV align="center">
  <TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
  <!-- Begin Table Head -->
  <TR valign="bottom">
      <TD width="47%">&nbsp;</TD>
      <TD width="5%">&nbsp;</TD>
      <TD width="47%">&nbsp;</TD>
  </TR>
  <!-- End Table Head -->
  <!-- Begin Table Body -->
  <TR valign="bottom">
      <TD align="center" valign="top"><B>Delaware</B><BR>
  (State or Other Jurisdiction of Incorporation<BR>
  or Organization)
  </TD>
      <TD>&nbsp;</TD>
      <TD align="center" valign="top"><B>77-0602661</B><BR>
  (I.R.S. Employer<BR>
  Identification No.)</TD>
  </TR>
  <!-- End Table Body -->
  </TABLE>
  </DIV>
  
  <DIV align="center">
  <TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
  <!-- Begin Table Head -->
  <TR valign="bottom">
      <TD width="47%">&nbsp;</TD>
      <TD width="5%">&nbsp;</TD>
      <TD width="47%">&nbsp;</TD>
  </TR>
  <!-- End Table Head -->
  <!-- Begin Table Body -->
  <TR valign="bottom">
      <TD align="center" valign="top"><B>300 Third Street<BR>
  Cambridge, Massachusetts</B><BR>
  (Address of Principal Executive Offices)
  </TD>
      <TD>&nbsp;</TD>
      <TD align="center" valign="top"><B>02142</B><BR>
  (Zip Code)</TD>
  </TR>
  <!-- End Table Body -->
  </TABLE>
  </DIV>
  
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>2004 Stock Incentive Plan</B><BR>
  (Full Title of the Plan)
  </DIV>
  
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>John M. Maraganore, Ph.D.<BR>
  President and Chief Executive Officer<BR>
  Alnylam Pharmaceuticals, Inc.<BR>
  300 Third Street<BR>
  Cambridge, Massachusetts 02142</B><BR>
  (Name and Address of Agent For Service)<BR>
  <B>(617)&nbsp;551-8200</B><BR>
  (Telephone Number, Including Area Code, of Agent For Service)
  </DIV>
  
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>CALCULATION OF REGISTRATION FEE</B>
  </DIV>
  <DIV align="center">
  <TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
  <!-- Begin Table Head -->
  <TR valign="bottom">
      <TD width="1%">&nbsp;</TD>
      <TD width="39%">&nbsp;</TD>
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      <TD width="1%">&nbsp;</TD>
      <TD width="22%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD><!-- VRule -->
      <TD width="1%">&nbsp;</TD>
      <TD width="9%">&nbsp;</TD>
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      <TD width="1%">&nbsp;</TD>
      <TD width="15%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD><!-- VRule -->
      <TD width="1%">&nbsp;</TD>
      <TD width="5%">&nbsp;</TD>
  
      <TD width="1%">&nbsp;</TD>
  </TR><TR style="font-size: 1px" valign="bottom">
      <TD nowrap align="left" colspan="15" style="border-bottom: 3px solid #000000">&nbsp;</TD>
  </TR>
  <TR style="font-size: 8pt" valign="bottom">    <TD width="1%">&nbsp;</TD>
  
      <TD>&nbsp;</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">Proposed</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">Proposed</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
  </TR>
  <TR style="font-size: 8pt" valign="bottom">    <TD width="1%">&nbsp;</TD>
  
      <TD>&nbsp;</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">Maximum</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">Maximum</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">Amount of</TD>
      <TD width="1%">&nbsp;</TD>
  </TR>
  <TR style="font-size: 8pt" valign="bottom">    <TD width="1%">&nbsp;</TD>
  
      <TD nowrap align="center">Title of Securities</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">Amount to be</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">Offering Price</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">Aggregate</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">Registration</TD>
      <TD width="1%">&nbsp;</TD>
  </TR>
  <TR style="font-size: 8pt" valign="bottom">    <TD width="1%">&nbsp;</TD>
  
      <TD nowrap align="center">to be registered</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">Registered(1)</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">Per Share</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">Offering Price</TD>
      <TD style="border-right: 2px solid #000000">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center">Fee</TD>
      <TD width="1%">&nbsp;</TD>
  </TR>
  
  <!-- End Table Head -->
  <!-- Begin Table Body -->
  <TR valign="bottom">
      <TD width="1%" style="border-top: 2px solid #000000">&nbsp;</TD>
                      <TD style="border-top: 2px solid #000000"><DIV style="margin-left:15px; text-indent:-15px">Common Stock<br>
  (including associated
  Series&nbsp;A Junior Participating<br>
  Preferred Stock Rights),
  $0.01 par value per share</DIV></TD>
      <TD style="border-right: 2px solid #000000; border-top: 2px solid #000000">&nbsp;</TD>
      <TD style="border-top: 2px solid #000000">&nbsp;</TD>
      <TD align="center" valign="bottom" style="border-top: 2px solid #000000">1,042,442 shares (2)</TD>
      <TD style="border-right: 2px solid #000000; border-top: 2px solid #000000">&nbsp;</TD>
      <TD style="border-top: 2px solid #000000">&nbsp;</TD>
      <TD align="center" valign="bottom" style="border-top: 2px solid #000000">$8.96(3)</TD>
      <TD style="border-right: 2px solid #000000; border-top: 2px solid #000000">&nbsp;</TD>
      <TD style="border-top: 2px solid #000000">&nbsp;</TD>
      <TD align="center" valign="bottom" style="border-top: 2px solid #000000">$9,340,280(3)</TD>
      <TD style="border-right: 2px solid #000000; border-top: 2px solid #000000">&nbsp;</TD>
      <TD style="border-top: 2px solid #000000">&nbsp;</TD>
  
  <TD align="center" valign="bottom" style="border-top: 2px solid #000000">$1,100</TD>
      <TD width="1%" style="border-top: 2px solid #000000">&nbsp;</TD>
  </TR>
  <TR style="font-size: 1px" valign="bottom">
      <TD nowrap align="left" colspan="15" style="border-top: 3px solid #000000">&nbsp;</TD>
  </TR>
  
  <!-- End Table Body -->
  </TABLE>
  </DIV>
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="1%" nowrap align="left">(1)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>In accordance with Rule&nbsp;416 under the Securities Act of 1933, as amended, this registration
  statement shall be deemed to cover any additional securities that may from time to time be
  offered or issued to prevent dilution resulting from stock splits, stock dividends or similar
  transactions.</TD>
  </TR>
  
  </TABLE>
  </DIV>
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="1%" nowrap align="left">(2)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Consists of an additional 1,042,442 shares issuable under the 2004 Stock Incentive Plan, as
  amended, pursuant to the terms of such plan.</TD>
  </TR>
  
  </TABLE>
  </DIV>
  
  <DIV style="margin-top: 6pt">
  <TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  <TR valign="top" style="font-size: 10pt; color: #000000; background: transparent">
      <TD width="1%" nowrap align="left">(3)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Estimated solely for the purpose of calculating the registration fee pursuant to Rules 457(c)
  and 457(h) of the Securities Act of 1933, as amended, and based upon the average of the high
  and low prices of the Registrant&#146;s Common Stock as reported on the Nasdaq National Market on
  August&nbsp;9, 2005.
  </TD>
  </TR>
  </TABLE>
  </DIV>
  
  
  <DIV style="width: 100%; border-bottom: 1pt solid black; margin-top: 10pt; font-size: 1pt">&nbsp;</DIV>
  <DIV style="width: 100%; border-bottom: 2pt solid black; font-size: 1pt">&nbsp;</DIV>
  
  
  
  
  
  <P align="center" style="font-size: 10pt">&nbsp;
  </DIV>
  
  <!-- PAGEBREAK -->
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  <DIV style="font-family: 'Times New Roman',Times,serif">
  
  <!-- TOC -->
  <A name="toc"><DIV align="CENTER" style="page-break-before:always"><U><B>TABLE OF CONTENTS</B></U></DIV></A>
  
  <P><CENTER>
  <TABLE border="0" width="90%" cellpadding="0" cellspacing="0">
  <TR>
  	<TD width="3%"></TD>
  	<TD width="3%"></TD>
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  	<TD width="3%"></TD>
  	<TD width="3%"></TD>
  	<TD width="76%"></TD>
  </TR>
  <TR><TD colspan="9"><A HREF="#000">STATEMENT OF INCORPORATION BY REFERENCE</A></TD></TR>
  <TR><TD colspan="9"><A HREF="#001">SIGNATURES</A></TD></TR>
  <TR><TD colspan="9"><A HREF="#002">INDEX TO EXHIBITS</A></TD></TR>
  <TR><TD colspan="9"><A HREF="b56318apexv5w1.htm">EX-5.1 Opinion of Wilmer Cutler Pickering Hale and Dorr LLP</A></TD></TR>
  <TR><TD colspan="9"><A HREF="b56318apexv23w2.htm">EX-23.2 Consent of PricewaterhouseCoopers LLP</A></TD></TR>
  </TABLE>
  </CENTER>
  <!-- /TOC -->
  <P><HR noshade><P>
  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  
  <DIV style="margin-top: 6pt"><TABLE width="100%" border="0" cellpadding="0" cellspacing="0" style="font-size: 10pt">
  
  
  </TABLE>
  </DIV>
  
  <!-- link1 "STATEMENT OF INCORPORATION BY REFERENCE" -->
  <DIV align="left"><A NAME="000"></A></DIV>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>STATEMENT OF INCORPORATION BY REFERENCE</B>
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;This Registration Statement on Form S-8 incorporates by reference the contents of the
  Registration Statement on Form S-8, File No.&nbsp;333-116151, filed by the Registrant on June&nbsp;3, 2004
  relating to the Registrant&#146;s 2004 Stock Incentive Plan.
  </DIV>
  
  <P align="center" style="font-size: 10pt">&nbsp;
  </DIV>
  
  <!-- PAGEBREAK -->
  <P><HR noshade><P>
  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  
  <DIV style="font-family: 'Times New Roman',Times,serif">
  
  <!-- link1 "SIGNATURES" -->
  <DIV align="left"><A NAME="001"></A></DIV>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>SIGNATURES</B>
  </DIV>
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Pursuant to the requirements of the Securities Act of 1933, the registrant certifies that it
  has reasonable grounds to believe that it meets all of the requirements for filing on Form S-8 and
  has duly caused this registration statement to be signed on its behalf by the undersigned,
  thereunto duly authorized, in the City of Cambridge, Commonwealth of Massachusetts, on this 11th
  day of August, 2005.
  </DIV>
  
  <TABLE width="100%" border="0" cellspacing="0" cellpadding="0" style="font-size: 10pt">
  <TR>
      <TD width="48%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="1%">&nbsp;</TD>
      <TD width="35%">&nbsp;</TD>
      <TD width="15%">&nbsp;</TD>
  </TR>
  <TR>
      <TD valign="top" align="left">&nbsp;</TD>
      <TD colspan="3" align="left">ALNYLAM PHARMACEUTICALS, INC.<BR>
  &nbsp;</TD>
      <TD>&nbsp;</TD>
  </TR><TR>
      <TD align="left">&nbsp;</TD>
      <TD valign="top">By:&nbsp;&nbsp;</TD>
  
  <TD colspan="2" style="border-bottom: 1px solid #000000" align="left">/s/ John M. Maraganore
  &nbsp;</TD>
      <TD>&nbsp;</TD>
  </TR><TR>
      <TD align="left">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD colspan="2" align="left">John M. Maraganore,
  Ph.D.<BR>President and Chief Executive Officer</TD>
      </TR><TR>
      <TD align="left">&nbsp;</TD>
      <TD>&nbsp;</TD>
      <TD colspan="2" align="left">&nbsp;</TD>
      <TD>&nbsp;</TD>
  </TR>
  <TR>
      <TD colspan="5">&nbsp;</TD>
  </TR>
  </TABLE>
  
  <DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>POWER OF ATTORNEY AND SIGNATURES</B>
  </DIV>
  
  
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;We, the undersigned officers and directors of Alnylam Pharmaceuticals, Inc., hereby severally
  constitute and appoint John M. Maraganore and Barry E. Greene, and each of them singly, our true
  and lawful attorneys with full power to them, and each of them singly, to sign for us and in our
  names in the capacities indicated below, the registration statement on Form S-8 filed herewith and
  any and all subsequent amendments to said registration statement, and generally to do all such
  things in our names and on our behalf in our capacities as officers and directors to enable Alnylam
  Pharmaceuticals, Inc. to comply with the provisions of the Securities Act of 1933, as amended, and
  all requirements of the Securities and Exchange Commission, hereby ratifying and confirming our
  signatures as they may be signed by our said attorneys, or any of them, to said registration
  statement and any and all amendments thereto.
  </DIV>
  
  <DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;Pursuant to the requirements of the Securities Act of 1933, this registration statement has
  been signed by the following persons in the capacities and on the dates indicated.
  </DIV>
  <DIV align="center">
  <TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
  <!-- Begin Table Head -->
  <TR valign="bottom">
      <TD width="20%">&nbsp;</TD>
      <TD width="3%">&nbsp;</TD>
      <TD width="20%">&nbsp;</TD>
      <TD width="3%">&nbsp;</TD>
      <TD width="20%">&nbsp;</TD>
  </TR>
  <TR style="font-size: 8pt" valign="bottom">
      <TD nowrap align="center" style="border-bottom: 1px solid #000000"><B>Signature</B></TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" style="border-bottom: 1px solid #000000"><B>Title</B></TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" style="border-bottom: 1px solid #000000"><B>Date</B></TD>
  </TR>
  
  <!-- End Table Head -->
  <!-- Begin Table Body -->
  <TR valign="bottom">
      <TD align="center" nowrap valign="top">/s/ John M. Maraganore
  <DIV style="font-size: 1pt; border-bottom: 1px solid #000000">&nbsp;</DIV>
  John M. Maraganore, Ph.D.</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">
  President, Chief Executive
  Officer and Director (Principal
  executive officer)
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">August 11, 2005</TD>
  </TR>
  <TR valign="bottom" style="padding-top: 1em">
      <TD align="center" nowrap valign="top">/s/ Barry E. Greene
  <DIV style="font-size: 1pt; border-bottom: 1px solid #000000">&nbsp;</DIV>
  Barry E. Greene</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">
  Chief Operating Officer and
  Treasurer (Principal financial
  and accounting officer)
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">August 11, 2005</TD>
  </TR>
  <TR valign="bottom" style="padding-top: 1em">
      <TD align="center" nowrap valign="top">/s/ Peter Barrett
  <DIV style="font-size: 1pt; border-bottom: 1px solid #000000">&nbsp;</DIV>
  Peter Barrett, Ph.D.</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">
  Director
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">August 11, 2005</TD>
  </TR>
  <TR valign="bottom" style="padding-top: 1em">
      <TD align="center" nowrap valign="top">/s/ John E. Berriman
  <DIV style="font-size: 1pt; border-bottom: 1px solid #000000">&nbsp;</DIV>
  John E. Berriman</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">
  Director
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">August 11, 2005</TD>
  </TR>
  <TR valign="bottom" style="padding-top: 1em">
      <TD align="center" nowrap valign="top">/s/ John K. Clarke
  <DIV style="font-size: 1pt; border-bottom: 1px solid #000000">&nbsp;</DIV>
  John K. Clarke</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">
  Director
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">August 11, 2005</TD>
  </TR>
  <!-- End Table Body -->
  </TABLE>
  </DIV>
  
  
  <P align="center" style="font-size: 10pt">&nbsp;
  </DIV>
  
  <!-- PAGEBREAK -->
  <P><HR noshade><P>
  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  
  <DIV style="font-family: 'Times New Roman',Times,serif">
  
  <DIV align="center">
  <TABLE style="font-size: 10pt" cellspacing="0" border="0" cellpadding="0" width="100%">
  <!-- Begin Table Head -->
  <TR valign="bottom">
      <TD width="20%">&nbsp;</TD>
      <TD width="3%">&nbsp;</TD>
      <TD width="20%">&nbsp;</TD>
      <TD width="3%">&nbsp;</TD>
      <TD width="20%">&nbsp;</TD>
  </TR>
  <TR style="font-size: 8pt" valign="bottom">
      <TD nowrap align="center" style="border-bottom: 1px solid #000000"><B>Signature</B></TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" style="border-bottom: 1px solid #000000"><B>Title</B></TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" style="border-bottom: 1px solid #000000"><B>Date</B></TD>
  </TR>
  
  <!-- End Table Head -->
  <!-- Begin Table Body -->
  <TR valign="bottom" style="padding-top: 1em">
      <TD align="center" nowrap valign="top">&nbsp;
  <DIV style="font-size: 1pt; border-bottom: 1px solid #000000">&nbsp;</DIV>
  Paul R. Schimmel, Ph.D.</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">
  Director
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom" style="padding-top: 1em">
      <TD align="center" nowrap valign="top">/s/ Philip A. Sharp
  <DIV style="font-size: 1pt; border-bottom: 1px solid #000000">&nbsp;</DIV>
  Philip A. Sharp, Ph.D.</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">
  Director
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">August 11, 2005</TD>
  </TR>
  <TR valign="bottom" style="padding-top: 1em">
      <TD align="center" nowrap valign="top">&nbsp;
  <DIV style="font-size: 1pt; border-bottom: 1px solid #000000">&nbsp;</DIV>
  Kevin P. Starr</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">
  Director
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">&nbsp;</TD>
  </TR>
  <TR valign="bottom" style="padding-top: 1em">
      <TD align="center" nowrap valign="top">/s/ James L. Vincent
  <DIV style="font-size: 1pt; border-bottom: 1px solid #000000">&nbsp;</DIV>
  James L. Vincent</TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">
  Director
  </TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">August 11, 2005</TD>
  </TR>
  <!-- End Table Body -->
  </TABLE>
  </DIV>
  
  
  <P align="center" style="font-size: 10pt">&nbsp;
  </DIV>
  
  <!-- PAGEBREAK -->
  <P><HR noshade><P>
  <H5 align="left" style="page-break-before:always"><A HREF="#toc">Table of Contents</A></H5><P>
  
  <DIV style="font-family: 'Times New Roman',Times,serif"></DIV>
  
  <!-- link1 "INDEX TO EXHIBITS" -->
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  <TD nowrap align="left" style="border-bottom: 1px solid #000000"><B>Exhibit<br>No.</B></TD>
      <TD>&nbsp;</TD>
      <TD nowrap align="center" style="border-bottom: 1px solid #000000"><B>Description</B></TD>
  </TR>
  
  <!-- End Table Head -->
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      <TD valign="top"><DIV style="margin-left:0px; text-indent:-0px">4.1(1)<br>
  4.2(2)<br>
  4.3(3)<br>
  &nbsp;<br>
  &nbsp;<br>
  &nbsp;<br>
  5.1<br>
  23.1<br>
  23.2<br>
  24.1<br>
  </DIV></TD>
      <TD>&nbsp;</TD>
      <TD align="left" valign="top">Restated Certificate of Incorporation of the Registrant<br>
  Amended and Restated By-Laws of the Registrant<br>
  Right Agreement dated as of July&nbsp;13, 2005 between the Registrant and EquiServe Trust<br>
  Company, N.A., as Rights Agent, which includes as Exhibit&nbsp;A the Form of Certificate of<br>
  Designations of Series&nbsp;A Junior Participating Preferred Stock, as Exhibit&nbsp;B the Form of<br>
  Rights Certificate and as Exhibit&nbsp;C the Summary of Rights to Purchase Preferred Stock<br>
  Opinion of Wilmer Cutler Pickering Hale and Dorr LLP, counsel to the Registrant<br>
  Consent of Wilmer Cutler Pickering Hale and Dorr LLP (included in Exhibit&nbsp;5.1)<br>
  Consent of PricewaterhouseCoopers LLP<br>
  Power of attorney (included on the signature pages of this registration statement)</TD>
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      <TD width="1%" nowrap align="left">(1)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Previously filed with the Securities and Exchange Commission as an Exhibit to the
  Registrant&#146;s Quarterly Report on Form 10-Q (File No.&nbsp;000-50743) for the quarterly period ended
  June&nbsp;30, 2005 and incorporated herein by reference.</TD>
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      <TD width="1%">&nbsp;</TD>
      <TD>Previously filed with the Securities and Exchange Commission as an Exhibit to the
  Registrant&#146;s Registration Statement on Form S-1, as amended (File No.&nbsp;333-113162), and
  incorporated herein by reference.</TD>
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      <TD width="1%" nowrap align="left">(3)</TD>
      <TD width="1%">&nbsp;</TD>
      <TD>Previously filed with the Securities and Exchange Commission as an Exhibit to the
  Registrant&#146;s Current Report on Form 8-K filed on July&nbsp;14, 2005 (File No.&nbsp;000-50743) and
  incorporated herein by reference.</TD>
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text: sv8
  Table of Contents
  As
  filed with the Securities and Exchange Commission on August 11,
  2005
  Registration
  No. 333-_____
  UNITED STATES
  SECURITIES AND EXCHANGE COMMISSION
  WASHINGTON, D.C. 20549
  FORM S-8
  REGISTRATION STATEMENT UNDER
  THE SECURITIES ACT OF 1933
  Alnylam Pharmaceuticals, Inc.
  (Exact Name of Registrant as Specified in Its Charter)
  Delaware
  (State or Other Jurisdiction of Incorporation
  or Organization)
  77-0602661
  (I.R.S. Employer
  Identification No.)
  300 Third Street
  Cambridge, Massachusetts
  (Address of Principal Executive Offices)
  02142
  (Zip Code)
  2004 Stock Incentive Plan
  (Full Title of the Plan)
  John M. Maraganore, Ph.D.
  President and Chief Executive Officer
  Alnylam Pharmaceuticals, Inc.
  300 Third Street
  Cambridge, Massachusetts 02142
  (Name and Address of Agent For Service)
  (617) 551-8200
  (Telephone Number, Including Area Code, of Agent For Service)
  CALCULATION OF REGISTRATION FEE
  Proposed
  Proposed
  Maximum
  Maximum
  Amount of
  Title of Securities
  Amount to be
  Offering Price
  Aggregate
  Registration
  to be registered
  Registered(1)
  Per Share
  Offering Price
  Fee
  Common Stock
  (including associated
  Series A Junior Participating
  Preferred Stock Rights),
  $0.01 par value per share
  1,042,442 shares (2)
  $8.96(3)
  $9,340,280(3)
  $1,100
  (1)
  In accordance with Rule 416 under the Securities Act of 1933, as amended, this registration
  statement shall be deemed to cover any additional securities that may from time to time be
  offered or issued to prevent dilution resulting from stock splits, stock dividends or similar
  transactions.
  (2)
  Consists of an additional 1,042,442 shares issuable under the 2004 Stock Incentive Plan, as
  amended, pursuant to the terms of such plan.
  (3)
  Estimated solely for the purpose of calculating the registration fee pursuant to Rules 457(c)
  and 457(h) of the Securities Act of 1933, as amended, and based upon the average of the high
  and low prices of the Registrant's Common Stock as reported on the Nasdaq National Market on
  August 9, 2005.
  TABLE OF CONTENTS
  STATEMENT OF INCORPORATION BY REFERENCE
  SIGNATURES
  INDEX TO EXHIBITS
  EX-5.1 Opinion of Wilmer Cutler Pickering Hale and Dorr LLP
  EX-23.2 Consent of PricewaterhouseCoopers LLP
  Table of Contents
  STATEMENT OF INCORPORATION BY REFERENCE
  This Registration Statement on Form S-8 incorporates by reference the contents of the
  Registration Statement on Form S-8, File No. 333-116151, filed by the Registrant on June 3, 2004
  relating to the Registrant's 2004 Stock Incentive Plan.
  Table of Contents
  SIGNATURES
  Pursuant to the requirements of the Securities Act of 1933, the registrant certifies that it
  has reasonable grounds to believe that it meets all of the requirements for filing on Form S-8 and
  has duly caused this registration statement to be signed on its behalf by the undersigned,
  thereunto duly authorized, in the City of Cambridge, Commonwealth of Massachusetts, on this 11th
  day of August, 2005.
  ALNYLAM PHARMACEUTICALS, INC.
  By:
  /s/ John M. Maraganore
  John M. Maraganore,
  Ph.D.
  President and Chief Executive Officer
  POWER OF ATTORNEY AND SIGNATURES
  We, the undersigned officers and directors of Alnylam Pharmaceuticals, Inc., hereby severally
  constitute and appoint John M. Maraganore and Barry E. Greene, and each of them singly, our true
  and lawful attorneys with full power to them, and each of them singly, to sign for us and in our
  names in the capacities indicated below, the registration statement on Form S-8 filed herewith and
  any and all subsequent amendments to said registration statement, and generally to do all such
  things in our names and on our behalf in our capacities as officers and directors to enable Alnylam
  Pharmaceuticals, Inc. to comply with the provisions of the Securities Act of 1933, as amended, and
  all requirements of the Securities and Exchange Commission, hereby ratifying and confirming our
  signatures as they may be signed by our said attorneys, or any of them, to said registration
  statement and any and all amendments thereto.
  Pursuant to the requirements of the Securities Act of 1933, this registration statement has
  been signed by the following persons in the capacities and on the dates indicated.
  Signature
  Title
  Date
  /s/ John M. Maraganore
  John M. Maraganore, Ph.D.
  President, Chief Executive
  Officer and Director (Principal
  executive officer)
  August 11, 2005
  /s/ Barry E. Greene
  Barry E. Greene
  Chief Operating Officer and
  Treasurer (Principal financial
  and accounting officer)
  August 11, 2005
  /s/ Peter Barrett
  Peter Barrett, Ph.D.
  Director
  August 11, 2005
  /s/ John E. Berriman
  John E. Berriman
  Director
  August 11, 2005
  /s/ John K. Clarke
  John K. Clarke
  Director
  August 11, 2005
  Table of Contents
  Signature
  Title
  Date
  Paul R. Schimmel, Ph.D.
  Director
  /s/ Philip A. Sharp
  Philip A. Sharp, Ph.D.
  Director
  August 11, 2005
  Kevin P. Starr
  Director
  /s/ James L. Vincent
  James L. Vincent
  Director
  August 11, 2005
  Table of Contents
  INDEX TO EXHIBITS
  Exhibit
  No.
  Description
  4.1(1)
  4.2(2)
  4.3(3)
  5.1
  23.1
  23.2
  24.1
  Restated Certificate of Incorporation of the Registrant
  Amended and Restated By-Laws of the Registrant
  Right Agreement dated as of July 13, 2005 between the Registrant and EquiServe Trust
  Company, N.A., as Rights Agent, which includes as Exhibit A the Form of Certificate of
  Designations of Series A Junior Participating Preferred Stock, as Exhibit B the Form of
  Rights Certificate and as Exhibit C the Summary of Rights to Purchase Preferred Stock
  Opinion of Wilmer Cutler Pickering Hale and Dorr LLP, counsel to the Registrant
  Consent of Wilmer Cutler Pickering Hale and Dorr LLP (included in Exhibit 5.1)
  Consent of PricewaterhouseCoopers LLP
  Power of attorney (included on the signature pages of this registration statement)
  (1)
  Previously filed with the Securities and Exchange Commission as an Exhibit to the
  Registrant's Quarterly Report on Form 10-Q (File No. 000-50743) for the quarterly period ended
  June 30, 2005 and incorporated herein by reference.
  (2)
  Previously filed with the Securities and Exchange Commission as an Exhibit to the
  Registrant's Registration Statement on Form S-1, as amended (File No. 333-113162), and
  incorporated herein by reference.
  (3)
  Previously filed with the Securities and Exchange Commission as an Exhibit to the
  Registrant's Current Report on Form 8-K filed on July 14, 2005 (File No. 000-50743) and
  incorporated herein by reference.