Exhibit 99.2

                 FOURTH AMENDMENT TO LOAN AND SECURITY AGREEMENT
                                     BETWEEN
                                 HYBRIDON, INC.
                                       AND
                               SILICON VALLEY BANK


         This  Fourth  Amendment  is  made,  effective  as of  the  29th  day of
September,  1998, to that certain Loan and Security  Agreement between Hybridon,
Inc., a Delaware  corporation  with a principal place of business at 155 Fortune
Boulevard, Milford,  Massachusetts (the "Borrower") and Silicon Valley Bank (the
"Bank")  dated as of December 31, 1996, as amended by consent  letter  agreement
(the "Consent Letter") dated January 15, 1998 and by First Amendment to Loan and
Security  Agreement  dated  March  30,  1998  (the  "First  Amendment"),  Second
Amendment  to Loan and  Security  Agreement  dated April 16,  1998 (the  "Second
Amendment") and Third  Amendment to Loan and Security  Agreement dated September
18, 1998 (the "Third Amendment").  The Loan and Security Agreement as so amended
is hereinafter referred to as the "Loan Agreement".  Capitalized terms used, but
not defined in this Fourth Amendment shall have the meanings ascribed to them in
the Loan Agreement and ancillary  documents,  instruments and agreements,  or if
not so  defined,  shall  have  the  meanings  ascribed  to them  in the  Uniform
Commercial Code, or in the case of financial and accounting terms, in accordance
with generally accepted accounting principles.

                                    RECITALS

         Pursuant to the Third  Amendment,  the  Borrower and the Bank agreed to
temporarily  waive  compliance  by the Borrower  with the Tangible Net Worth and
Minimum  Liquidity   covenants  (as  amended)  through  September  29,  1998  to
accommodate  the sale by the Borrower of the CRLP  Interest.  The closing of the
sale of the CRLP Interest has not occurred and the Borrower has  requested  that
the Bank agree to extend the waiver of  covenant  compliance  until  October 31,
1998.

         The Bank is willing to  consent to extend the  temporary  waiver of the
Minimum Liquidity and Tangible Net Worth covenants,  but only upon the terms and
conditions set forth in this Fourth Amendment.

                                    AGREEMENT

         In  consideration  of  the  foregoing,  and  of  the  undertakings  and
obligations of the Borrower and the Bank set forth herein and for other good and
valuable   consideration,   receipt   and   sufficiency   of  which  are  hereby
acknowledged, the Borrower and Bank agree as follows:

     1.   The Borrower  confirms that the  outstanding  balance of principal and
          interest  on the  Loan  as of  October  15,  1998 is as set  forth  in
          Schedule 1 hereto,  and that the  Borrower  has no  defense,  claim or
          offset which would preclude full payment of such amount.

     2.   The Borrower  ratifies and confirms:  (i) its  Obligations to the Bank
          under  the  Loan  Agreement,  as  amended  hereby,  (ii)  all  of  the
          representations  and  warranties  made  by it in the  Loan  Agreement,
          except as  expressly  disclosed  to the Bank,  and (iii) that it is in
          compliance with




          the covenants and agreements  contained in the Loan  Agreement  except
          for its failure to maintain  compliance  with the covenants  waived in
          the First Amendment, its failure to comply with Section 6.10(c) of the
          Loan  Agreement,  to the extent that such failure is  nevertheless  in
          compliance with the Intellectual  Property Security Agreement (the "IP
          Security Agreement")  delivered by the Borrower in connection with the
          Consent Letter (it being agreed that the provisions of Section 6.10(c)
          shall be  deemed  superseded  by the  analogous  provisions  of the IP
          Security Agreement),  and except for Borrower's failure to comply with
          the Minimum  Liquidity and Tangible Net Worth covenants as of June 30,
          1998 and thereafter.

     3.   The Bank hereby waives any existing  defaults in the Minimum Liquidity
          and Tangible Net Worth  covenants  and also waives  compliance  by the
          Borrower with the Minimum  Liquidity and Tangible Net Worth  covenants
          through October 31, 1998; provided however,  that if the CRLP Put Date
          is earlier  than  October 31, 1998,  testing of such  covenants  shall
          begin on the  following  business  day after the CRLP Put Date  rather
          than on October 31, 1998.  Within two (2) business days after the CRLP
          Put  Date,  the  Borrower  will pay to the Bank in good and  collected
          funds,  in  addition  to  any  regularly  scheduled  payments  on  the
          Obligations,  the sum of $750,000 as an additional payment against the
          principal of the Obligations.

     4.   In  consideration  of the  Bank's  agreement  to extend  its waiver of
          compliance with the Tangible Net Worth and Liquidity covenants through
          October 31, 1998, the Borrower shall pay to the Bank a forbearance fee
          in the amount of $25,000 in  addition  to any other  amounts  due with
          respect to the Obligations.  If the CRLP Put Date is after October 15,
          1998, the  forbearance fee shall increase by $1,000 per day commencing
          October 16, 1998, but in no event more than an additional $16,000. The
          $25,000  installment of the  forbearance fee is due and payable on the
          date of this Fourth Amendment,  and any and all incremental  increases
          thereto shall be due and payable no later than October 31, 1998.

     5.   The Borrower further  acknowledges  that all reasonable  out-of-pocket
          costs  and  expenses  of  he  Bank  in  connection  with  negotiation,
          documentation and  administration of this Fourth Amendment,  including
          reasonable fees of attorneys  engaged to represent the Bank,  shall be
          borne by the Borrower.

     6.   The Borrower  acknowledges  and  confirms  that to the extent that the
          Borrower  may have any claims,  offsets,  counterclaims,  or defenses,
          asserted or unasserted, the Borrower, for itself, and on behalf of its
          successors,   assigns,  parents,  subsidiaries,   agents,  affiliates,
          predecessors,  employees, officers, directors, executors and heirs, as
          applicable  (collectively,  the  "Borrower  Affiliates")  releases and
          forever discharges the Bank, its subsidiaries,  affiliates, employees,
          officers,  directors, agents, successors and assigns, both present and
          former  (collectively,  the "Bank Affiliates") of and from any and all
          manner  of  claims,  offsets,  counterclaims,   defenses,  action  and
          actions,  cause and causes of  action,  suits,  debts,  controversies,
          damages,  judgments,  executions, and demands whatsoever,  asserted or
          unasserted,  in law or in equity,  which  against  the Bank and/or the
          Bank  Affiliates,  they or the  Borrower  Affiliates  ever  had to and
          including  the date  hereof,  upon or by reason of any matter,  cause,
          causes or thing whatsoever,  in connection with the Loan and/or any of
          the  transactions   and  matters  related  thereto,   except  for  the
          obligations of the Bank in such documents,  instruments and agreements
          to be performed after the date of this Fourth Amendment.  The Borrower
          shall indemnify, defend


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          and hold the Bank harmless of and from any claim brought or threatened
          against the Bank by the  Borrower or any other person (as well as from
          attorneys'  fees and expenses in  connection  therewith) on account of
          the Loan  Agreement,  the Note, the Consent Letter,  the  Intellectual
          Property   Security   Agreement,   Pledge   Agreement,   Intercreditor
          Agreement,  the  First  Amendment,  the  Second  Amendment,  the Third
          Amendment, this Fourth Amendment and any other document, instrument or
          agreement   given  in  connection   with  the  Loan  and  any  of  the
          transactions  and  matters  related  thereto  (each  of  which  may be
          defended, compromised,  settled or pursued by the Bank with counsel of
          the Bank's election reasonably acceptable to the Borrower,  but at the
          expense of the Borrower),  except in the case of the Bank's failure to
          comply  with  its  obligations  hereunder  or  thereunder,  its  gross
          negligence or willful misconduct.

     7.   The Borrower  acknowledges and agrees that the Bank's agreement herein
          to  temporarily  waive  compliance  with  the  Minimum  Liquidity  and
          Tangible Net Worth  covenants  shall not create a course of dealing or
          conduct  and that the Bank has not agreed to waive any other  covenant
          or agreement with the Borrower or to waive compliance with the Minimum
          Liquidity and Tangible Net Worth  covenants other than for the limited
          time period set forth in this Fourth Amendment.

     8.   To the extent possible, this Fourth Amendment shall be construed to be
          consistent with the provisions of the Loan Agreement;  however, to the
          extent that the provisions of this Fourth Amendment expressly conflict
          with  or  contradict  the  provisions  of  the  Loan  Agreement,   the
          provisions of this Fourth Amendment shall be deemed to control.

     9.   This Fourth  Amendment  represents  the entire  agreement  between the
          parties with respect to the modifications  contained herein, and shall
          be  construed  in  accordance  with  the laws of the  Commonwealth  of
          Massachusetts as an agreement under seal. The Borrower has voluntarily
          entered into this Fourth  Amendment  without coercion or duress of any
          kind and has been or has had the opportunity to have been  represented
          by legal counsel of its choosing.


         WITNESS  OUR  hands  and  seals  on this  30th  day of  October,  1998,
effective as of September 29, 1998.



WITNESS:                                            SILICON VALLEY BANK

/s/ C. Wade                                        By: /s/ Sean Lynden
- - -----------------------------                          ------------------------

                                                       HYBRIDON, INC.

/s/ Cheryl M. Northrup                             By: /s/ E. Andrews Grinstead
- - -----------------------------                          ------------------------


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                                  SCHEDULE 1 TO
                 FOURTH AMENDMENT TO LOAN AND SECURITY AGREEMENT
                                     BETWEEN
                               SILICON VALLEY BANK
                               AND HYBRIDON, INC.

Principal Balance as of October 15, 1998                      $2,832,289.22
Interest outstanding at October 15, 1998                          14,613.83


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